METHODS FOR TREATMENT OF DEGENERATIVE RETINAL DISEASES

Abstract: Provided are methods for obtaining in vivo expression of a polynucleotide sequence placed under the control of a retinal pigment epithelial (RPE) cell- or Muller cell-specific promoter in mammalian host organisms. Genetic constructs comprising an RPE or Muller cell-specific promoter and a degradation-inhibitor nucleotide sequence are introduced into the subretinal space of the host and specifically expressed in RPE cells or Muller cells.

Description: DESCRIPTION METHODS FOR TREATMENT OF DEGENERATIVE RETINAL DISEASES BACKGROUND OF THE INVENTION The present application claims the benefit of the priority date of co-pending U.S. Patent Application Serial No. 09/156,084, filed September 17, 1998, the entire text of which is specifically incorporated herein by reference without disclaimer. The government owns rights in the present invention pursuant to grant number EY07864 from the National Institutes of Health. 1. Field of the Invention The present invention relates generally to the fields of molecular biology and diseases of the eye. More particularly, it concerns compositions and methods for the prevention or treatment of apoptosis or necrosis of retinal photoreceptor cells. 2. Description of Related Art Modern techniques of molecular biology and genetics have enabled many new areas of research and clinical application to be developed. DNA constructs can now be assembled and moved from host to host to enable the expression of natural or constructed foreign genes in any number of host organisms. It has also become possible to design systems to regulate, either up or down, the abundance of native proteins in tissues of host organisms. The term gene therapy is used to refer to the delivery of one or more genetic constructs into a host, typically a human or an animal model, for the purpose of treating a disease or condition or causing some other genetic change to the animal. The techniques of gene therapy are under active research and clinical development and examples now exist of human patients who have received clinical relief from serious conditions following gene therapy. Effective gene therapy requires both a competent genetic construct, as well as an effective delivery system. A wide variety of delivery systems are known based on mechanical, chemical or biological delivery of the genetic construct to the tissue in the individual to be affected. The most common gene delivery systems are based on the use of highly modified viruses that have the native ability to deliver genetic message, whether in DNA or in RNA, directly into living cells. Any number of viral vector systems are known to the gene therapy scientific community, as well as techniques for their use. To construct a competent genetic construct requires both a nucleotide coding sequence coding for the expression of either a protein or an antisense RNA, and appropriate regulatory sequences so that the coding sequence is expressed in the needed abundance in the appropriate tissues. The most important regulatory sequence is often the promoter, which initiates gene expression. Promoters can be constitutive, in which case they express the coding sequence which follows in any cell type in which they reside, or can be tissue or developmentally specific, meaning that the promoter interacts with other gene regulation elements in the cells, known or unknown, so that the promoter only drives expression of the coding sequence in certain cell types or in cells in certain developmental stages. Since it is an objective of gene therapy techniques to deliver the expression product to the cells having the disease or condition and to avoid, to the extent practical, generation of the gene product in non-targeted tissues, selection of appropriate delivery systems and regulatory elements for specific targeted cells is highly desirable. Each year, thousands of people suffer loss of vision as a result of degenerative diseases of the retina such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity (ROP). In the United States alone, an estimated 100,000 people are affected by RP, and between 1,000,000 and 1,700,000 suffer from AMD. Although diseases of the retina may have disparate genetic and biochemical causes, at a biochemical level they apparently share a common pathway of degeneration. In each case, loss of vision is caused primarily by the degeneration of rod and/or cone photoreceptor cells. Degeneration is initiated by exposure to a critical level of stress (e.g., oxidative stress, accumulation of degradative by-products), that causes the cells to enter an apoptotic or necrotic pathway that ultimately results in the death of photoreceptor cells. What is needed to prevent loss of vision in people affected by diseases of the retina is effective means of preventing or reducing the degeneration of photoreceptor cells. Thus, compositions and methods that are effective in the prevention and/or treatment of retinal photoreceptor cell apoptosis or necrosis would represent a significant advance in the art. SUMMARY OF THE INVENTION The present invention overcomes one or more of these and other shortcomings in the art by providing compositions and methods that are effective in the prevention and/or treatment of retinal photoreceptor cell apoptosis or necrosis. The present invention provides genetic constructs comprising a promoter that is preferentially expressed in retinal pigment epithelial (RPE) cells operably connected to a gene product-encoding DNA sequence that encodes a photoreceptor degradation-inhibitory agent that is not natively associated with the promoter. Thus, the present invention provides compositions and methods for obtaining targeted expression of a DNA sequence that encodes a photoreceptor degradation-inhibitory agent in retinal pigment epithelial or Muller cells. It is one object of the present invention to prevent or reduce degeneration of photoreceptor cells by this targeted expression of a DNA sequence that encodes a photoreceptor degradation-inhibitory agent in retinal pigment epithelial or Muller cells. The present invention provides DNA constructs comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a first DNA sequence that encodes a photoreceptor degradation-inhibitory agent. As used herein, the term "photoreceptor degradation-inhibitory agent" will be understood to include DNA sequences, the expression of which result in gene products that slow or prevent degeneration of the photoreceptor cells exposed to the product. The expression product may be a polypeptide, or polypeptide cleavage product thereof, that is effective in slowing or preventing degeneration of photoreceptor cells. The expression product may also be an antisense RNA or ribozyme that interferes with the synthesis of a polypeptide involved in the degeneration of photoreceptor cells. In preferred aspects of the invention, the promoter is a cellular retinaldehyde- binding protein gene, an 11-cis retinol dehydrogenase gene or a RPE 65 gene promoter. In certain embodiments, the promoter is an 11-cis retinol dehydrogenase gene promoter having the sequence from between about nucleotide 1 to about nucleotide 528 of SEQ ID NO: 1, while in other embodiments the promoter is an 11-cis retinol dehydrogenase gene promoter having the sequence of SEQ ID NO: 1. In other embodiments of the invention, the promoter is a cellular retinaldehyde- binding protein gene promoter having the sequence of SEQ ID NO: 2. In yet other embodiments, the promoter is an RPE 65 gene promoter having the sequence of SEQ ID NO: 3. In further embodiments of the invention, the DNA sequence encodes a photoreceptor degradation-inhibitory protein, exemplified by, but not limited to, a ciliary neurotrophic factor, a brain derived neurotrophic factor, a fibroblast growth factor, a neurotrophin, a cytokine, a neural growth factor or one of the anti-apoptotic agents listed in Table 1. In other aspects of the present invention, the DNA construct comprises a second DNA sequence that encodes a secretory peptide, wherein the secretory sequence and the DNA sequence are linked as a single transcriptional unit that encodes a fusion protein comprising the secretory peptide linked to the photoreceptor degradation-inhibitory agent. Exemplary secretory peptides contemplated for use in the present invention include, but are not limited to, an immunoglobulin G secretory peptide, a human growth factor secretory peptide or an IL-7 secretory peptide. In certain aspects of the invention, the DNA construct is comprised within a recombinant vector. In preferred aspects of the invention, the DNA construct is comprised within a recombinant viral vector, exemplified by, but not limited to, recombinant adeno-associated viral vectors and recombinant retroviral vectors. In further embodiments, the recombinant viral vectors are comprised within a recombinant virus, such as a recombinant adeno-associated virus or a recombinant retrovirus. In embodiments of the present invention involving administration of the DNA construct to an animal, the DNA construct is preferably dispersed in a pharmaceutically acceptable excipient. Thus, pharmaceutical compositions comprising the disclosed DNA constructs are also provided by the present invention. The present invention further provides recombinant vectors comprising a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation- inhibitory agent. In preferred aspects of the invention, the recombinant vector is a recombinant viral vector, and in particularly preferred aspects, the recombinant viral vector is a recombinant adeno-associated viral vector. The present invention also provides recombinant viruses comprising a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation- inhibitory agent. In preferred embodiments, the recombinant virus is a recombinant adeno-associated virus. Thus, the present invention also provides recombinant adeno-associated viruses comprising a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation-inhibitory agent. The DNA constructs, as described herein, may be used for treating or preventing retinal cell photoreceptor apoptosis or necrosis. In preferred embodiments, the retinal cell photoreceptor apoptosis or necrosis is associated with retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, optic neuritis or retinopathy of prematurity. Use of the DNA constructs, vectors or viruses provided herein in the manufacture of a medicament for treating or preventing retinal cell photoreceptor apoptosis or necrosis is also provided by the present invention. In preferred embodiments, the medicament is intended for treating or preventing retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy or retinopathy of prematurity. The present invention additionally provides kits comprising, in a suitable container, one or more of the DNA constructs provided herein. In certain aspects, the kits comprise a second, distinct ophthalmic therapeutic composition. Additionally provided by the present invention are methods for inhibiting apoptosis or necrosis in retinal photoreceptor cells, comprising contacting retinal pigment epithelial or Muller cells with a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation-inhibitory agent. The present invention thus also provides methods for obtaining in vivo cell-specific expression of a desired sequence in retinal pigment epithelial cells in a mammalian host organism, comprising providing a genetic construct comprising a retinal pigment epithelial or Muller cell-specific promoter operably linked or connected to a polynucleotide coding sequence not natively associated with the promoter, the coding sequence coding for the expression of a gene product which interferes with the process of apoptosis or necrosis in photoreceptor cells, and delivering the construct to retinal pigment epithelial cells of the host organism. In certain methods, the DNA construct is comprised within a viral vector, the viral vector administered to the retinal pigment epithelial or Muller cells. In preferred methods, the DNA construct is comprised within an adeno-associated viral vector, the adeno-associated viral vector administered to the retinal pigment epithelial or Muller cells. In preferred methods of the present invention, the retinal pigment epithelial or Muller cells are comprised within an animal, exemplified by, but not limited to, a human subject. In other methods, the retinal photoreceptor cell apoptosis or necrosis is associated with retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, optic neuritis or retinopathy of prematurity. BRIEF DESCRIPTION OF THE DRAWINGS Not Applicable DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS Certain aspects of the present invention involve a gene therapy approach based on gene delivery and expression in non-affected target cells. In diseases such as RP and AMD, it is the photoreceptor cells of the retina, the rod and cone cells, which are affected and which undergo apoptosis or necrosis to cause the observed clinical symptoms. In the methods described herein, genetic constructs expressing proteins intended to avoid apoptosis or necrosis are delivered to the retinal pigment epithelium and Muller cells, the constructs being designed for strong gene expression in retinal pigment epithelium cells (RPE) and the Muller cells. These epithelial cells, which surround and support the photoreceptive neuron cells, can be induced to express degradation-inhibiting agents at high levels, and the levels of these agents in the retinal pigment epithelium and Muller cells will lessen the rate of apoptosis or necrosis of the photoreceptor cells. Delivering the genetic constructs to neighboring RPE or Muller cells avoids the difficulty inherent in targeting gene expression to the photoreceptor cells themselves, many of which could be dead or weakened once the clinical symptom of the disease has become apparent. The problems associated with using gene therapy to deliver a DNA sequence to degenerating photoreceptor cells may be ameliorated by delivering the therapeutic DNA sequence under the control of an RPE- and Muller cell-specific promoter to retinal pigment epithelial cells and Muller glial cells. RPE cells and Muller cells are vitally important in maintaining and nourishing the rod and cone photoreceptor cells. Both cell types provide important metabolic support for primary light detectors (rod and cone photoreceptor cells), and for horizontal, bipolar, and ganglion cells, which are involved in processing secondary neural signals. In certain of the methods of the present invention, healthy, unaffected RPE cells are targeted for specific expression of a therapeutic DNA sequence. Retinal pigment epithelial cells and Muller cells are selected for targeting, because high expression of gene products by these cells will deliver degradation-inhibitory expression products to photoreceptor cells, in a manner analogous to the normal function of these cells, which normally provide nutrients and 11-cis retinaldehyde to photoreceptor cells. Therapeutic expression products of a degradation-inhibitory DNA sequence expressed in transfected RPE or Muller cells are transported to neighboring photoreceptor cells and slow degeneration of the photoreceptor cells. To validate this approach, the inventors demonstrated cell-specific gene expression in rat RPE cells using the reporter gene green fluorescent protein (GFP) under the control of a RPE cell-specific promoter. As described in detail in the examples, injection of a solution comprising recombinant viral vector (1 x 10 12 viral particles/ml) having a GFP reporter gene operably connected to an RPE cell-specific promoter into the subretinal space of rats resulted in high efficiency transfection of RPE cells. The reporter gene was not expressed in photoreceptor cells. In the examples below, rats were used as the mammalian host organism to evaluate RPE cell-specific expression of a reporter gene under the control of an RPE cell-specific promoter following subretinal injection of the rats. It is reasonably expected that the present invention could be successfully employed in any mammalian species, including humans. Gene therapy techniques similar to those described here are usually developed in animal model species. The retinal structure and biochemical functioning of rats is consistent with those of common mammals, including humans. To be effective in improving the patient's condition, the genetic construct of the present invention should preferably include a coding sequence effective to express a gene product which is effective to inhibit or delay apoptosis or necrosis in photoreceptor cells. Several protein agents have been identified as having potential for such effect. One promising agent is ciliary neurotrophic factor (CNTF), which has been shown to promote the survival of several classes of neurons and glia (Henderson et al. 1994). Other potential agents that could act to slow or inhibit apoptosis or necrosis include neurotrophines, cytokines, or other neural growth factors. In mouse animal models, intravitreal injection of CNTF, brain-derived neurotrophic factor (BDNF), or axokine was found to protect photoreceptor cells against degeneration (LaVail, et al. 1998). It is not a requirement that the gene product expressed by the genetic construct completely inhibit apoptosis or necrosis. It is sufficient for some relief to the affected individual if the gene product has the effect of either partially inhibiting or delaying the apoptotic or necrotic processes. Any delay in the progression of such degenerative diseases would be welcome to an individual with the condition. The genetic treatment methods of the present invention are based on the delivery and expression of genetic constructions to the retinal pigment epithelium. While it is preferred that a viral vector, particularly an adeno-associated viral vector, be used to deliver the genetic construct to the targeted RPE or Muller cells, it is recognized that expression of the genetic construct in those cells is the object, and the method by which the genetic construct is delivered to those cells is of lesser importance. Several other techniques are contemplated to deliver genetic constructs into patients including retroviral vectors, liposomes, particle mediated gene delivery and naked DNA injection. One of skill in the art would appreciate that although a certain minimum virus titer may be required to achieve efficient transfection, there is a range of virus titers that may be effectively employed. Preferably, the virus titer of the injected material is at least 1 x 10 12 viral particles/ml. I. Retinal Cell-Specific Promoters The following sequences were tested and found to promote RPE cell-specific gene expression in vivo: 1) a 528-bp promoter region (bases 1-528 of SEQ ID NO:l) of a murine 11-cis retinol dehydrogenase (RDH) gene (Driessen et al., 1995; Simon et al, 1995 ; Simon et al, 1996; Genbank Accession Number X97752); 2) a 2274-bp promoter region (SEQ ID NO:2) from a human cellular retinaldehyde-binding protein (CRALBP) gene (Intres et al, 1994; Kennedy et al, 1998; Genbank Accession Number L34219); and 3) a 1485-bρ promoter region (SEQ ID NO:3) from human RPE65 (Nicoletti et al, 1998, Genbank Accession Number U20510). The Examples below demonstrate that SEQ ID NO:l, SEQ ID NO:2, or SEQ ID NO: 3 promote retinal pigment epithelial cell-specific expression of GFP. It is envisioned that minor variations from SEQ ID NO:l, SEQ ID NO:2, or SEQ ID NO:3 associated with nucleotide additions, deletions, and mutations, whether naturally occurring or introduced in vitro, will not affect cell-specificity. Furthermore, it is expected and envisioned that other promoters will be discovered that also are characterized by abundant and/or specific expression in RPE or Muller cells, and the use of such promoters is specifically envisioned in the present invention. II. Photoreceptor Cell Degradation-Inhibitory Agents Among the preferred photoreceptor cell degradation-inhibitory agents for use in the present invention are neurotrophic factors. Neurotrophic factors are natural proteins, found in the nervous system or in non-nerve tissues innervated by the nervous system, that function to promote the survival and maintain the phenotypic differentiation of certain nerve and/or glial cell populations (Varon et al, 1978; Thoenen et al, 1985). Because of this physiological role, neurotrophic factors are useful in treating the degeneration of such nerve cells and the loss of differentiated function that results from nerve damage. The first neurotrophic factor to be identified was nerve growth factor (NGF). NGF is the first member of a defined family of trophic factors, called the neurotrophins, that currently includes brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, and NT-6 (Thoenen, 1991; Snider, 1994; Bothwell, 1995). These neurotrophins are known to act via the family of trk tyrosine kinase receptors, i.e., trkA, trkB, trkC, and the low affinity p75 receptor (Snider, 1994; Bothwell, 1995; Chao et al, 1995). Additional neurotrophic factors have been identified, including ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF). Exemplary anti-photoreceptor cell necrosis or apoptosis compounds contemplated for use in the present invention include ciliary neurotrophic factor (CNTF), brain derived neurotrophic factor (BNDF), acidic and basic fibroblast growth factor (FGF), glial cell line-derived neurotrophic factor (GDNF) proteins, human apoptosis inhibitor 1 (GenBank accession number NM_001165), human apoptosis inhibitor 2 (GenBank accession number NM_001166), human apoptosis inhibitor 3 (GenBank accession number NM_001167), and inhibitors of apoptosis proteins (LAP), proteins that inhibit capsase, including the human X-linked inhibitor of apoptosis protein (XIAP; GenBank accession number U45880) and human neuronal inhibitor of apoptosis protein (NIAP; GenBank accession number U19251). Ciliary neurotrophic factor (CNTF) is a protein that is specifically required for the survival of embryonic chick ciliary ganglion neurons in vitro (Manthorpe et al, 1980). The ciliary ganglion is anatomically located within the orbital cavity, lying between the lateral rectus and the sheath of the optic nerve. It receives parasympathetic nerve fibers from the oculomotor nerve, which innervate the ciliary muscle and sphincter pupillae. Human CNTF has been identified and found to be a 200 amino acid protein with a molecular weight of 22,931 (Swiss-Prot Accession Number P26441). CNTF has been cloned and sequenced from a number of organisms, including human (GenBank accession numbers X60542, NM_000614), pig (Sus scrofa, GenBank accession number U57644), rat (GenBank accession number XI 7457), and rabbit (GenBank accession number M29828). Additional CNTF sequences for use in the present invention are described in U.S. Patent Nos. 5,846,935, 5,593,857, 5,780,600, 5,349,056, 5,141,856, 5,011,914 and 4,997,929, each of which is incorporated herein in its entirety by reference. Using pig brain as a starting material, Barde et al. (1982) reported a factor, now termed brain-derived neurotrophic factor (BDNF), which appeared to promote the survival of dorsal root ganglion neurons from ElO/El 1 chick embryos. BDNF has been cloned and sequenced from a wide variety of organisms, including human (GenBank accession numbers X60201, M61176, M37762, NM_001709), rhesus monkey (Macaca mulatto, GenBank accession number X61475), mouse (Mus musculus, GenBank accession number X55573), rat (GenBank accession numbers D10938, M61178, M61175), pig (Sus scrofa, GenBank accession number X16713), cow (Bos taurus, GenBank accession number X97914), guinea pig (Cavia porcellus, GenBank accession number AB012097), raccoon (Procyon lotor, GenBank accession number AF003188), Malayan sun bear (Helarctos malayanus, GenBank accession number AF002240), brown bear (Ursus arctos, GenBank accession number AF002239), giant panda (Ailuropoda melanoleuka, GenBank accession number U56638), lesser panda (Ailurus fulgens, GenBank accession number U56639), chicken (Gallus gallus, GenBank accession numbers X91250, M83377), echidna (Tachyglossus aculeatus, GenBank accession number U93383), kowari (Dasyuroides byrnei, GenBank accession number U93382), western grey kangaroo (Macropus fuliginosus, GenBank accession number U93381), marsupial mole (Notorpetes typhlops, GenBank accession number U93380), common brush tailed possum (Trichosurus vulpecula, GenBank accession number U93379), pygmy possum (Cercartetus lapidus, GenBank accession number U93378), sugar glider (Petaurus breviceps, GenBank accession number U93377), duckbill platypus (Ornithorhynchus anatinus, GenBank accession number U93376), honey possum (Tarsipes rostratus, GenBank accession number U93375), northern brown bandicoot (Isoodon macrourus, GenBank accession number U93374), marbled lungfish (Protopterus aethiopicus, GenBank accession number U93369), South American short-tailed grey opossum (Monodelphis domestica, GenBank accession number U95024), marbled electric ray (Torpedo marmorata, GenBank accession number X99276), zebrafish (Danio rerio, GenBank accession number U42489), carp (Cyprinus carpio, GenBank accession numbers L27171, AF008558), southern platyfish (Xiphophorus maculatus, GenBank accession numbers X59942, S40501), and African clawed frog (Xenopus laevis, GenBank accession number X61477). BDNF sequences contemplated for use in certain embodiments of the present invention include those described in U.S. Patent Nos. 5,438,121 and 5,229,500, each of which is incorporated herein in their entirety by reference. Fibroblast growth factor (FGF) was first separated as a factor exhibiting strong growth promoting action on fibroblasts such as BALB/c-3T3 cells (Gospodarowicz, 1974). At present, FGF is known to have a growth promoting effect on almost all mesoderm-derived cells. The fibroblast growth factor (FGF) family is comprised of at least 20 structurally related proteins (FGFs 1-20), whose best known members are acidic FGF (aFGF; FGF-1) and basic FGF (bFGF; FGF-2). Acidic FGF has been characterized from a number of animals, including human (GenBank accession numbers E03692, AH004637, S74129 and S74128), mouse (GenBank accession numbers M30641, U36455, U36459, U36457, U67610 and AF012926), bovine (GenBank accession numbers M97660, M97661, M13439) and newt (U.S. Patent No. 5,750,365, incorporated herein by reference). Basic FGF has also been cloned and sequenced from a variety of organisms, including human (GenBank accession numbers X04432, X04433, M27968 and Y13468), rat (GenBank accession numbers M22427 and U78079), mouse (GenBank accession number M30644), bovine (GenBank accession number M13440), domestic sheep (Ovis aries, GenBank accession number L36136), newt (Cynops pyrrhogaster, GenBank accession number D89443) and Xenopus laevis (GenBank accession number M18067). In addition to the acidic and basic FGF, a large number of other FGF family members have been cloned and sequenced, including FGF3 from chicken (GenBank accession number Z47555) and Xenopus laevis (GenBank accession number X65237), FGF4 from human (GenBank accession numbers NM_002008 and NM_002007) and mouse (GenBank accession number U43515), FGF5 from human (GenBank accession numbers NM_004464, AH005423, M23534, M23535, M23536, M37825 and AB016517), rat (GenBank accession numbers D64085 and D64086) and mouse (GenBank accession numbers AH003595, AB016516, M30643, M37821, M37822 and M37823), FGF6 from human (GenBank accession numbers X14072, X14073 and X63454) and mouse (GenBank accession numbers X51552, X51553 and X51554), FGF7 from human (GenBank accession number L06242), rat (GenBank accession number X95743) and mouse (GenBank accession number Z22703), FGF8 from human (GenBank accession numbers NM_006119, D38752, AH003682, U36223, U36225, U36226, U36228, U56978 and AB014615), dog (GenBank accession number AF022487), mouse (GenBank accession numbers Z48746 and U18673), chicken (GenBank accession number U55189) and zebrafish (GenBank accession number AF034264), FGF9 from human (GenBank accession number D 14838), mouse (GenBank accession numbers D38258, S82023 and U33535), rat (GenBank accession number D 14839) and Xenopus laevis (GenBank accession number U47622), FGF 10 from human (GenBank accession number AB002097) and rat (GenBank accession number D79215), FGF 11 from human (GenBank accession numbers NM_004112, Z70275), FGF 12 from human (GenBank accession numbers U76381 and Z70276) and mouse (GenBank accession numbers AF020738, AF020739 and AF020740), FGF 13 from mouse (GenBank accession number AF020737), FGF 14 from human (GenBank accession number NM_004115), FGF 15 from mouse (GenBank accession number AF007268), FGF16 from human (GenBank accession numbers NM_003868 and AB009391) and rat (GenBank accession number AB002561), FGF17 from human (GenBank accession numbers NM_003867 and AB009249), mouse (GenBank accession number AB009250) and rat (GenBank accession number AB008682), FGF 18 from human (GenBank accession numbers NM_003862, AB075292 and AB007422), mouse (GenBank accession numbers AF075291 and AB004639) and rat (GenBank accession number AB004638), FGF 19 from human (GenBank accession numbers AF 110400, NM_005117 and AB018122) and FGF20 from Xenopus laevis (GenBank accession number ABO 12615). Additionally, Xenopus laevis embryonic FGF (GenBank accession numbers X62593 and X62594), C. elegans FGF (GenBank accession number U85766) and other human FGF sequences (GenBank accession numbers X04431 and X59065) are contemplated for use in certain aspects of the invention. Furthermore, a number of useful FGF sequences have been disclosed in U.S Patents, including human bFGF analogs (U.S. Patent No. 5,859,208 incorporated herein by reference), bFGF muteins (U.S. Patent Nos. 5,852,177 and 5,851,990, each incorporated herein by reference), stabilized FGF (U.S. Patent Nos. 5,849,722 and 5,314,872, each incorporated herein by reference), stabilized FGF pharmaceutical compositions (U.S. Patent Nos. 5,714,458, 5,348,941 and 5,217,954, each incorporated herein by reference), recombinant human and bovine FGF (U.S. Patent Nos. 5,604,293 and 5,439,818, each incorporated herein by reference), glycosylated FGF (U.S. Patent Nos. 5,464,943 and 5,360,896, each incorporated herein by reference), bovine bFGF (U.S. Patent No. 5,464,774, incorporated herein by reference), human aFGF (U.S. Patent No. 5,395,756, incorporated herein by reference), acidic FGF (U.S. Patent No. 5,401,832, incorporated herein by reference), active fragments of bFGF (U.S. Patent No. 5,387,673, incorporated herein by reference), mutant bFGF (U.S. Patent No. 5,352,589, incorporated herein by reference), cysteine modified aFGF (U.S. Patent Nos. 5,409,897, 5,312,911 and 5,223,483, each incorporated herein by reference), chimeric FGF (U.S. Patent Nos. 5,310,883 and 5,302,702, each incorporated herein by reference), bFGF fragments (U.S. Patent No. 5,206,354, incorporated herein by reference) and bovine FGF (U.S. Patent No. 4,956,455, incorporated herein by reference). GDNF is a protein that may be identified in or obtained from glial cells and that exhibits neurotrophic activity. More specifically, GDNF is a dopaminergic neurotrophic protein that is characterized in part by its ability to increase dopamine uptake on the embryonic precursors of the substantia nigra dopaminergic neurons, and further by its ability to promote the survival of parasympathetic and sympathetic nerve cells. GDNF has been cloned and sequenced from a variety of organisms, including human (GenBank accession numbers LI 9063, AJ001896, AF053749, AF 053748, NM_000514 and AF063586), rhesus monkey (Macaca mulatto, GenBank accession number AF 106678), mouse (Mus musculus, GenBank accession numbers D83350, D83351, D83352, D88264, D49921, U36449, U66196, U75532 and U37459) and rat (GenBank accession numbers X92495 and LI 5305). Additionally, alternative forms of GDNF from human have been described, including HFB1 (GenBank accession number AJ001900), HFK2 (GenBank accession number AJ001899), HFK4 (GenBank accession number AJ001898) and HFK3 (GenBank accession number AJ001897). GDNF sequences are also described in U.S. Patent No. 5,935,795, incorporated herein by reference. Other exemplary anti-photoreceptor cell necrosis or apoptosis genes and constructs are listed herein in Table 1. Any one or more of the genes listed therein may be used alone, or in combination with the ciliary neurotrophic factor (CNTF), brain derived neurotrophic factor (BNDF) and fibroblast growth factor (FGF) proteins disclosed herein. It will be understood that the genes listed in Table 1 are only exemplary of the types of the anti-photoreceptor cell necrosis or apoptosis genetic constructs and elements that may be used in this invention. Further anti-photoreceptor cell necrosis or apoptosis genes and constructs will be known to those of ordinary skill in the art. Table 1 Exemplary Anti-Cell Death/Anti-Apoptosis Agents Table 1 (con't.) A. DNA Compositions Important aspects of the present invention concern isolated DNA segments and recombinant vectors encoding photoreceptor cell degradation inhibitory agents, such as ciliary neurotrophic factor (CNTF), brain derived neurotrophic factor (BNDF) and fibroblast growth factor (FGF) proteins, and the creation and use of recombinant host cells through the application of DNA technology, that express photoreceptor cell degradation inhibitory agents, using the nucleic acid sequences disclosed herein. DNA segments, recombinant vectors, recombinant host cells and expression methods involving the photoreceptor cell degradation inhibitory sequences are also provided. Each of the foregoing sequences are included within all aspects of the following description. The present invention concerns DNA segments, isolatable from mammalian cells, that are free from total genomic DNA and that are capable of expressing a photoreceptor cell degradation inhibitory protein or polypeptide. As used herein, the term "DNA segment" refers to a DNA molecule that has been isolated free of total genomic DNA of a particular species. Therefore, for example, a DNA segment encoding a photoreceptor cell degradation inhibitory protein refers to a DNA segment that contains photoreceptor cell degradation inhibitory protein coding sequences yet is isolated away from, or purified free from, total genomic DNA. Included within the term "DNA segment", are DNA segments and smaller fragments of such segments, and also recombinant vectors, including, for example, plasmids, cosmids, phage, viruses, and the like. Similarly, a DNA segment comprising an isolated or purified photoreceptor cell degradation inhibitory gene refers to a DNA segment including wild-type, polymorphic or mutant photoreceptor cell degradation inhibitory protein coding sequences and, in certain aspects, regulatory sequences, isolated substantially away from other naturally occurring genes or protein encoding sequences. In this respect, the term "gene" is used for simplicity to refer to a functional protein, polypeptide or peptide-encoding unit. As will be understood by those in the art, this functional term includes both genomic sequences, cDNA sequences and smaller engineered gene segments that express, or may be adapted to express, proteins, polypeptides, domains, peptides, fusion proteins and mutants. "Isolated substantially away from other coding sequences" means that the gene of interest, for example a photoreceptor cell degradation inhibitory gene, forms the significant part of the coding region of the DNA segment, and that the DNA segment does not contain large portions of naturally-occurring coding DNA, such as large chromosomal fragments or other functional genes or protein coding regions. Of course, this refers to the DNA segment as originally isolated, and does not exclude genes or coding regions later added to the segment by the hand of man. In particular embodiments, the invention concerns isolated DNA segments and recombinant vectors incorporating DNA sequences that encode, for example, a photoreceptor cell degradation inhibitory protein or peptide, that includes within its amino acid sequence a contiguous amino acid sequence in accordance with, or essentially as set forth in, the amino acid sequences disclosed herein, corresponding to wild-type, polymorphic or mutant photoreceptor cell degradation inhibitory proteins. The term "a sequence essentially as set forth in" means that the sequence substantially corresponds to a portion of the disclosed amino acid sequence, and has relatively few amino acids that are not identical to, or a biologically functional equivalent of, the amino acids of the disclosed amino acid sequence. The term "biologically functional equivalent" is well understood in the art and is further defined in detail herein. Accordingly, sequences that have between about 70% and about 80%; or more preferably, between about 81% and about 90%; or even more preferably, between about 91% and about 99%; of amino acids that are identical or functionally equivalent to the amino acids of the disclosed sequences will be sequences that are "essentially as set forth in" the disclosed amino acid sequences, provided the biological activity of the protein is maintained. In certain other embodiments, the invention concerns isolated DNA segments and recombinant vectors that include within their sequence a nucleic acid sequence essentially as set forth in the nucleic acid sequences disclosed herein. The term "essentially as set forth in" is used in the same sense as described above and means that the nucleic acid sequence substantially corresponds to a portion of the disclosed nucleic acid sequence and has relatively few codons that are not identical, of functionally equivalent, to the codons of the disclosed nucleic acid sequence. The term "functionally equivalent codon" is used herein to refer to codons that encode the same amino acid, such as the six codons for arginine or serine, and also refers to codons that encode biologically equivalent amino acids (see Table 2). It will also be understood that amino acid and nucleic acid sequences may include additional residues, such as additional N- or C-terminal amino acids or 5' or 3' sequences, and yet still be essentially as set forth in one of the sequences disclosed herein, so long as the sequence meets the criteria set forth above, including the maintenance of biological protein activity where protein expression is concerned. The addition of terminal sequences particularly applies to nucleic acid sequences that may, for example, include various non-coding sequences flanking either of the 5' or 3' portions of the coding region or may include various internal sequences, i.e., introns, which are known to occur within genes. Excepting flanking regions, and allowing for the degeneracy of the genetic code, sequences that have between about 70% and about 79%; or more preferably, between about 80% and about 89%; or even more preferably, between about 90% and about 99%; of nucleotides that are identical to the nucleotides of the disclosed nucleic acid sequences will be sequences that are "essentially as set forth in" these sequences. Sequences that are essentially the same as those set forth in the disclosed nucleic acid sequences may also be functionally defined as sequences that are capable of hybridizing to a nucleic acid segment containing the complement of the disclosed nucleic acid sequences under relatively stringent conditions. Suitable relatively stringent hybridization conditions will be well known to those of skill in the art, as disclosed herein. For applications requiring high selectivity, one will typically desire to employ relatively stringent conditions to form the hybrids, e.g., one will select relatively low salt and/or high temperature conditions, such as provided by about 0.02 M to about 0.10 M NaCl at temperatures of about 50°C to about 70°C. Such high stringency conditions tolerate little, if any, mismatch between the probe and the template or target strand, and would be particularly suitable for isolating specific genes or detecting specific mRNA transcripts. It is generally appreciated that conditions can be rendered more stringent by the addition of increasing amounts of formamide. For certain applications, for example, substitution of nucleotides by site-directed mutagenesis, it is appreciated that lower stringency conditions are required. Under these conditions, hybridization may occur even though the sequences of probe and target strand are not perfectly complementary, but are mismatched at one or more positions. Conditions may be rendered less stringent by increasing salt concentration and decreasing temperature. For example, a medium stringency condition could be provided by about 0.1 to 0.25 M NaCl at temperatures of about 37°C to about 55°C, while a low stringency condition could be provided by about 0.15 M to about 0.9 M salt, at temperatures ranging from about 20°C to about 55°C. Thus, hybridization conditions can be readily manipulated depending on the desired results. In other embodiments, hybridization may be achieved under conditions of, for example, 50 mM Tris-HCl (pH 8.3), 75 mM KC1, 3 mM MgCl 2 , 1.0 mM dithiothreitol, at temperatures between approximately 20°C to about 37°C. Other hybridization conditions utilized could include approximately 10 mM Tris-HCl (pH 8.3), 50 mM KC1, 1.5 mM MgCl 2 , at temperatures ranging from approximately 40°C to about 72°C. Another exemplary, but not limiting, standard hybridization is incubated at 42°C in 50% formamide solution containing dextran sulfate for 48 hours and subjected to a final wash in 0.5X SSC, 0.1% SDS at 65°C. Naturally, the present invention also encompasses DNA segments that are complementary, or essentially complementary, to the sequence set forth in the disclosed nucleic acid sequences. Nucleic acid sequences that are "complementary" are those that are capable of base-pairing according to the standard Watson-Crick complementarity rules. As used herein, the term "complementary sequences" means nucleic acid sequences that are substantially complementary, as may be assessed by the same nucleotide comparison set forth above, or as defined as being capable of hybridizing to the disclosed nucleic acid sequences under relatively stringent conditions such as those described herein. The nucleic acid segments of the present invention, regardless of the length of the coding sequence itself, may be combined with other DNA sequences, such as promoters, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, and the like, such that their overall length may vary considerably. It is therefore contemplated that a nucleic acid fragment of almost any length may be employed, with the total length preferably being limited by the ease of preparation and use in the intended recombinant DNA protocol. For example, nucleic acid fragments may be prepared that include a short contiguous stretch identical to or complementary to the disclosed nucleic acid sequences, such as about 8, about 10 to about 14, or about 15 to about 20 nucleotides, and that are up to about 20,000, or about 10,000, or about 5,000 base pairs in length, with segments of about 3,000 being preferred in certain cases. DNA segments with total lengths of about 1,000, about 500, about 200, about 100 and about 50 base pairs in length (including all intermediate lengths) are also contemplated to be useful. It will be readily understood that "intermediate lengths", in these contexts, means any length between the quoted ranges, such as 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.; 21, 22, 23, etc.; 30, 31, 32, etc.; 50, 51, 52, 53, etc.; 100, 101, 102, 103, etc.; 150, 151, 152, 153, etc.; including all integers through the 200-500; 500- 1,000; 1,000-2,000; 2,000-3,000; 3,000-5,000; 5,000-10,000 ranges, up to and including sequences of about 12,001, 12,002, 13,001, 13,002, 15,000, 20,000 and the like. The various antisense primers designed around the disclosed nucleotide sequences of the present invention may be of any length. By assigning numeric values to a sequence, for example, the first residue is 1, the second residue is 2, etc., an algorithm defining all primers can be proposed: n to n + y where n is an integer from 1 to the last number of the sequence and y is the length of the primer minus one, where n + y does not exceed the last number of the sequence. Thus, for a 10-mer, the probes correspond to bases 1 to 10, 2 to 11, 3 to 12 ... and so on. For a 15-mer, the probes correspond to bases 1 to 15, 2 to 16, 3 to 17 ... and so on. For a 20- mer, the probes correspond to bases 1 to 20, 2 to 21, 3 to 22 ... and so on. It will also be understood that this invention is not limited to the particular disclosed nucleic acid and amino acid sequences. Recombinant vectors and isolated DNA segments may therefore variously include these coding regions themselves, coding regions bearing selected alterations or modifications in the basic coding region, or they may encode larger polypeptides that nevertheless include such coding regions or may encode biologically functional equivalent proteins or peptides that have variant amino acids sequences. Certain of the DNA segments of the present invention encompass biologically functional equivalent proteins and peptides. Such sequences may arise as a consequence of codon redundancy and functional equivalency that are known to occur naturally within nucleic acid sequences and the proteins thus encoded. Alternatively, functionally equivalent proteins or peptides may be created via the application of recombinant DNA technology, in which changes in the protein structure may be engineered, based on considerations of the properties of the amino acids being exchanged. Changes designed by man may be introduced through the application of site-directed mutagenesis techniques, e.g., to introduce improvements to the antigenicity of the protein or to test mutants in order to examine DNA binding activity at the molecular level. One may also prepare fusion proteins and peptides, e.g., where the protein coding regions are aligned within the same expression unit with other proteins or peptides having desired functions, such as for secretion, purification or immunodetection purposes (e.g., proteins that may be purified by affinity chromatography and enzyme label coding regions, respectively). Encompassed by the invention are DNA segments encoding relatively small peptides, such as, for example, peptides of from about 15 to about 50 amino acids in length, and also larger polypeptides up to and including proteins corresponding to the full-length amino acid sequences as set forth in herein. B. Amino Acid Compositions The present invention therefore provides purified, and in preferred embodiments, substantially purified, photoreceptor cell degradation inhibitory protein and peptides, for example ciliary neurotrophic factor (CNTF), brain derived neurotrophic factor (BNDF) and fibroblast growth factor (FGF) proteins and peptides. The term "purified photoreceptor cell degradation inhibitory protein or peptide", as used herein, is intended to refer to, for example, a wild-type, polymorphic or mutant photoreceptor cell degradation inhibitory proteinaceous composition, isolatable from mammalian cells or recombinant host cells, wherein the wild-type, polymorphic or mutant photoreceptor cell degradation inhibitory protein or peptide is purified to any degree relative to its naturally-obtainable state, i.e., relative to its purity within a cellular extract. A purified photoreceptor cell degradation inhibitory protein or peptide therefore also refers to a photoreceptor cell degradation inhibitory protein or peptide free from the environment in which it naturally occurs. Proteins for use in the present invention may be full length proteins, while in certain aspects of the invention they may also be less then full length proteins, such as individual domains, regions or even epitopic peptides. Generally, "purified" will refer to, for example, a photoreceptor cell degradation inhibitory protein or peptide composition that has been subjected to fractionation to remove various non-wild-type, polymorphic or mutant photoreceptor cell degradation inhibitory protein or peptide components, and which composition substantially retains its photoreceptor cell degradation inhibitory activity. Where the term "substantially purified" is used, this will refer to a composition in which the protein or peptide forms the major component of the composition, such as constituting about 50% of the proteins in the composition or more. In preferred embodiments, a substantially purified protein will constitute more than 60%, 70%, 80%, 90%, 95%o, 99% or even more of the proteins in the composition. A polypeptide or protein that is "purified to homogeneity," as applied to the present invention, means that the polypeptide or protein has a level of purity where the polypeptide or protein is substantially free from other proteins and biological components. For example, a purified polypeptide or protein will often be sufficiently free of other protein components so that degradative sequencing may be performed successfully. Various methods for quantifying the degree of purification the disclosed proteins or peptides will be known to those of skill in the art in light of the present disclosure. These include, for example, determining the number of polypeptides within a fraction by gel electrophoresis. Assessing the number of polypeptides within a fraction by SDS/PAGE analysis will often be preferred in the context of the present invention as this is straightforward. To purify a protein or peptide, such as a photoreceptor cell degradation inhibitory protein or peptide, a natural or recombinant composition comprising at least some photoreceptor cell degradation inhibitory proteins or peptides will be subjected to fractionation to remove various non-photoreceptor cell degradation inhibitory protein or peptide components from the composition. Various techniques suitable for use in protein purification will be well known to those of skill in the art. These include, for example, precipitation with ammonium sulfate, PEG, antibodies and the like or by heat denaturation, followed by centrifugation; chromatography steps such as ion exchange, gel filtration, reverse phase, hydroxylapatite, and affinity chromatography; isoelectric focusing; gel electrophoresis; and combinations of such and other techniques. Another example is the purification of a fusion protein using a specific binding partner. Such purification methods are routine in the art. This is currently exemplified by the generation of a glutathione S-transferase fusion protein, expression in E. coli, and isolation to homogeneity using affinity chromatography on glutathione- agarose. Although preferred for use in certain embodiments, there is no general requirement that the disclosed proteins or peptides always be provided in their most purified state. Indeed, it is contemplated that less substantially purified proteins or peptides, which are nonetheless enriched in, for example, photoreceptor cell degradation inhibitory protein or peptide compositions, relative to the natural state, will have utility in certain embodiments. Methods exhibiting a lower degree of relative purification may have advantages in total recovery of protein product, or in maintaining the activity of an expressed protein. Inactive products also have utility in certain embodiments, such as, e.g., in antibody generation. In certain embodiments of the present invention, the photoreceptor cell degradation inhibitory compositions of the invention are fusion proteins prepared by molecular biological techniques. Fusion proteins are ' polypeptides that comprise two or more regions derived from different, or heterologous, proteins or peptides. The use of recombinant DNA techniques to achieve such ends is now standard practice to those of skill in the art. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques and in vivo recombination/genetic recombination. DNA and RNA synthesis may, additionally, be performed using an automated synthesizers. In general, to prepare a fusion protein, one would join at least a first DNA coding region, such as a gene or cDNA, encoding at least a first peptide or polypeptide to at least a second DNA coding region (i.e., gene or cDNA) encoding at least a second peptide or polypeptide. This typically involves preparing an expression vector that comprises, in the same reading frame, a first DNA segment encoding the first peptide or polypeptide operatively linked to a second DNA segment encoding the second peptide or polypeptide. The sequences are attached in a manner such that translation of the total nucleic acid yields the desired fusion proteins of the invention. Expression vectors contain one or more promoters upstream of the inserted DNA regions that act to promote transcription of the DNA and to thus promote expression of the encoded recombinant protein. This is the meaning of "recombinant expression". When produced via recombinant DNA techniques, the photoreceptor cell degradation inhibitory compounds of the invention that are capable of being secreted from a cell, such as a retinal pigment epithelial or Muller cell, are referred to as "fusion proteins". It is to be understood that such fusion proteins contain, at least, a photoreceptor cell degradation inhibitory sequence and a secretion sequence as defined in this invention, and that these sequences are operatively attached. The fusion proteins may also include additional peptide sequences, such as antigenic sequences, involved in the identification and/or purification of the fusion protein, so long as such additional sequences do not appreciably affect the activities of the resultant fusion protein. C. Antisense In an alternative embodiment, the photoreceptor cell degradation inhibitory nucleic acids employed may actually encode antisense constructs that hybridize, under intracellular conditions, to nucleic acids encoding proteins involved in apoptosis or necrosis of photoreceptor cells. The term "antisense construct" is intended to refer to nucleic acids, preferably oligonucleotides, that are complementary to the base sequences of a target DNA or RNA. Antisense oligonucleotides, when introduced into a target cell, specifically bind to their target nucleic acid and interfere with transcription, RNA processing, transport, translation and/or stability. Antisense constructs may be designed to bind to the promoter and other control regions, exons, introns or even exon-intron boundaries of a gene. Antisense RNA constructs, or DNA encoding such antisense RNA's, may be employed to inhibit gene transcription or translation or both within a host cell, either in vitro or in vivo, such as within a host animal, including a human subject. Nucleic acid sequences which comprise "complementary nucleotides" are those which are capable of base- pairing according to the standard Watson-Crick complementarity rules. That is, that the larger purines will base pair with the smaller pyrimidines to form combinations of guanine paired with cytosine (G:C) and adenine paired with either thymine (A:T), in the case of DNA, or adenine paired with uracil (A:U) in the case of RNA. Inclusion of less common bases such as inosine, 5-methylcytosine, 6-methyladenine, hypoxanthine and others in hybridizing sequences does not interfere with pairing. As used herein, the terms "complementary" means nucleic acid sequences that are substantially complementary over their entire length and have very few base mismatches. For example, nucleic acid sequences of fifteen bases in length may be termed complementary when they have a complementary nucleotide at thirteen or fourteen positions with only a single mismatch. Naturally, nucleic acid sequences that are "completely complementary" will be nucleic acid sequences that are entirely complementary throughout their entire length and have no base mismatches. Other sequences with lower degrees of homology also are contemplated. For example, an antisense construct that has limited regions of high homology, but also contains a non-homologous region (e.g., a ribozyme) could be designed. These molecules, though having less than 50% homology, would bind to target sequences under appropriate conditions. While all or part of the gene sequence may be employed in the context of antisense construction, short oligonucleotides are easier to make and increase in vivo accessibility. However, both binding affinity and sequence specificity of an antisense oligonucleotide to its complementary target increases with increasing length. One can readily determine whether a given antisense nucleic acid is effective at targeting of the corresponding host cell gene simply by testing the constructs in vitro to determine whether the function of the endogenous gene is affected or whether the expression of related genes having complementary sequences is affected. In certain embodiments, one may wish to employ antisense constructs that include other elements, for example, those which include C-5 propyne pyrimidines. Oligonucleotides that contain C-5 propyne analogues of uridine and cytidine have been shown to bind RNA with high affinity and to be potent antisense inhibitors of gene expression. III. Recombinant Expression Recombinant vectors form further aspects of the present invention. Particularly useful vectors are contemplated to be those vectors in which the coding portion of a photoreceptor cell degradation inhibitory DNA segment, whether encoding a full length protein or smaller peptide, is positioned under the control of a promoter. For expression in this manner, one would position the coding sequences adjacent to and under the control of the promoter. It is understood in the art that to bring a coding sequence under the control of a promoter, one positions the 5' end of the transcription initiation site of the transcriptional reading frame of the protein between about 1 and about 50 nucleotides "downstream" of (i.e., 3' of) the chosen promoter. The promoter may be in the form of the promoter that is naturally associated with a particular retinal pigment epithelial cell- or Muller cell-specific gene, as may be obtained by isolating the 5' non-coding sequences located upstream of the coding segment, for example, using recombinant cloning and/or PCR™ technology, in connection with the compositions disclosed herein. Direct amplification of nucleic acids using the PCR™ technology of U.S. Patents 4,683,195 and 4,683,202 (herein incorporated by reference) are particularly contemplated to be useful in such methodologies. In other embodiments, it is contemplated that certain advantages will be gained by positioning the coding DNA segment under the control of a recombinant, or heterologous, retinal pigment epithelial cell- or Muller cell-specific promoter. As used herein, a recombinant or heterologous retinal pigment epithelial cell- or Muller cell-specific promoter is intended to refer to a promoter that is not normally associated with a particular photoreceptor cell degradation inhibitory gene in its natural environment. The promoters employed may be constitutive, or inducible, and can be used under the appropriate conditions to direct high level expression of the introduced DNA segment, such as is advantageous in the large-scale production of recombinant proteins or peptides. It will, of course, be understood that one or more than one genes encoding photoreceptor cell degradation inhibitory proteins and/or or peptides may be used in the methods and compositions of the invention. The nucleic acid compositions and methods disclosed herein may entail the administration of one, two, three, or more, genes or gene segments. The maximum number of genes that may be used is limited only by practical considerations, such as the effort involved in simultaneously preparing a large number of gene constructs or even the possibility of eliciting a significant adverse cytotoxic effect. In using multiple genes, they may be combined on a single genetic construct under control of one or more promoters, or they may be prepared as separate constructs of the same of different types. Thus, an almost endless combination of different genes and genetic constructs may be employed. Certain gene combinations may be designed to, or their use may otherwise result in, achieving synergistic effects on the prevention or reduction of retinal photoreceptor cell apoptosis or necrosis. Any and all such combinations are intended to fall within the scope of the present invention. Where eukaryotic expression is contemplated, one will also typically desire to incorporate into the transcriptional unit an appropriate polyadenylation site (e.g., 5'-AATAAA-3') if one was not contained within the original cloned segment. Typically, the poly-A addition site is placed about 30 to 2000 nucleotides "downstream" of the termination site of the protein at a position prior to transcription termination. In connection with expression embodiments to prepare recombinant photoreceptor cell degradation inhibitory proteins and peptides, it is contemplated that longer DNA segments will most often be used, with DNA segments encoding the entire protein or functional domains, epitopes, ligand binding domains, subunits, etc. being most preferred. However, it will be appreciated that the use of shorter DNA segments to direct the expression of antisense constructs also fall within the scope of the invention. As used herein, the term "engineered" or "recombinant" cell is intended to refer to a cell into which a recombinant gene, such as a gene encoding a photoreceptor cell degradation inhibitory protein or peptide, has been introduced. Therefore, engineered cells are distinguishable from naturally occurring cells that do not contain a recombinantly introduced gene. Engineered cells are thus cells having a gene or genes introduced through the hand of man. Recombinantly introduced genes will either be in the form of a single structural gene, an entire genomic clone comprising a structural gene and flanking DNA, or an operon or other functional nucleic acid segment which may also include genes positioned either upstream and/or downstream of the promoter, regulatory elements, or structural gene itself, or even genes not naturally associated with the particular structural gene of interest. These recombinant host cells may be employed in connection with "overexpressing" photoreceptor cell degradation inhibitory proteins, that is, increasing the level of expression over that found naturally in retinal pigment epithelial or Muller cells. However, there is no requirement that a highly purified vector be used, so long as the coding segment employed encodes a protein or peptide of interest, and does not include any coding or regulatory sequences that would have an adverse effect on cells. Therefore, it will also be understood that useful nucleic acid sequences may include additional residues, such as additional non-coding sequences flanking either of the 5' or 3' portions of the coding region or may include various regulatory sequences. It is further contemplated that the photoreceptor cell degradation inhibitory proteins or epitopic peptides derived from native or recombinant photoreceptor cell degradation inhibitory proteins may be "overexpressed", i.e., expressed in increased levels relative to its natural expression, or even relative to the expression of other proteins in a recombinant host cell containing photoreceptor cell degradation inhibitory protein-encoding DNA segments. Such overexpression may be assessed by a variety of methods, including radiolabeling and/or protein purification. However, simple and direct methods are preferred, for example, those involving SDS/PAGE and protein staining or Western blotting, followed by quantitative analyses, such as densitometric scanning of the resultant gel or blot. A specific increase in the level of the recombinant protein or peptide in comparison to the level in retinal pigment epithelial or Muller cells is indicative of overexpression, as is a relative abundance of the specific protein in relation to the other proteins produced by the host cell and, e.g., visible on a gel. It will be further understood that certain of the polypeptides may be present in quantities below the detection limits of the Coomassie brilliant blue staining procedure usually employed in the analysis of SDS/PAGE gels, or that their presence may be masked by an inactive polypeptide of a similar molecular weight. Although not necessary to the routine practice of the present invention, it is contemplated that other detection techniques may be employed advantageously in the visualization of particular polypeptides of interest. Immunologically-based techniques such as Western blotting using enzymatically-, radiolabel-, or fluorescently-tagged antibodies are considered to be of particular use in this regard. Alternatively, the proteins and peptides of the present invention may be detected by using primary antibodies having affinity for the photoreceptor cell degradation inhibitory proteins or peptides in combination with secondary antibodies having affinity for such primary antibodies. This secondary antibody may be enzymatically- or radiolabeled, or alternatively, fluorescently-, or colloidal gold-tagged. Means for the labeling and detection of such two-step secondary antibody techniques are well-known to those of skill in the art. IV. DNA Delivery In various embodiments of the invention, DNA is delivered to a cell as an expression construct. Several non-viral methods for the transfer of expression constructs into cultured mammalian cells also are contemplated by the present invention. These include calcium phosphate precipitation, DEAE-dextran, electroporation, direct microinjection, DNA-loaded liposomes and lipofectamine- DNA complexes, cell sonication, gene bombardment using high velocity microprojectiles, and receptor-mediated transfection. Some of these techniques may be successfully adapted for in vivo or ex vivo use, as discussed below. In another embodiment of the invention, the expression construct may simply consist of naked recombinant DNA or plasmids. Transfer of the construct may be performed by any of the methods mentioned above which physically or chemically permeabilize the cell membrane. This is particularly applicable for transfer in vitro, but it may be applied to in vivo use as well. Another embodiment of the invention for transferring a naked DNA expression construct into cells may involve particle bombardment. This method depends on the ability to accelerate DNA coated microprojectiles to a high velocity allowing them to pierce cell membranes and enter cells without killing them. Several devices for accelerating small particles have been developed. One such device relies on a high voltage discharge to generate an electrical current, which in turn provides the motive force. The microprojectiles used have consisted of biologically inert substances such as tungsten or gold beads. In a further embodiment of the invention, the expression construct may be entrapped in a liposome, as discussed below. Also contemplated are lipofectamine- DNA complexes. Liposome-mediated nucleic acid delivery and expression of foreign DNA in vitro has been very successful. Wong et al. (1980) demonstrated the feasibility of liposome-mediated delivery and expression of foreign DNA in cultured chick embryo, HeLa and hepatoma cells. In certain embodiments of the invention, the liposome may be complexed with a hemagglutinating virus (HVJ). This has been shown to facilitate fusion with the cell membrane and promote cell entry of liposome- encapsulated DNA. In other embodiments, the liposome may be complexed or employed in conjunction with nuclear non-histone chromosomal proteins (HMG-1). In yet further embodiments, the liposome may be complexed or employed in conjunction with both HVJ and HMG-1. In other embodiments, the delivery vehicle may comprise a ligand and a liposome. Where a bacterial promoter is employed in the DNA construct, it also will be desirable to include within the liposome an appropriate bacterial polymerase. However, the preferred method for delivery of the expression constructs to the retinal pigment epithelial or Muller cells is via viral delivery. The ability of certain viruses to enter cells via receptor-mediated endocytosis and to integrate into host cell genome and express viral genes stably and efficiently have made them attractive candidates for the transfer of foreign genes into mammalian cells. Preferred gene therapy vectors of the present invention will generally be viral vectors. Adeno-associated virus (AAV) is particularly attractive for gene transfer because it does not induce any pathogenic response and can integrate into the host cellular chromosome (Kotin et al, 1990). The AAV terminal repeats (TRs) are the only essential cw-components for the chromosomal integration (Muzyczka and McLaughin, 1988). These TRs are reported to have promoter activity (Flotte et al, 1993). They may promote efficient gene transfer from the cytoplasm to the nucleus or increase the stability of plasmid DNA and enable longer-lasting gene expression. Studies using recombinant plasmid DNAs containing AAV TRs have attracted considerable interest. AAV-based plasmids have been shown to drive higher and longer transgene expression than the identical plasmids lacking the TRs of AAV in most cell types (Shafron et al, 1998). AAV (Ridgeway, 1988; Hermonat and Muzyczka, 1984) is a parovirus, discovered as a contamination of adenoviral stocks. It is a ubiquitous virus (antibodies are present in 85% of the US human population) that has not been linked to any disease. It is also classified as a dependovirus, because its replication is dependent on the presence of a helper virus, such as adenovirus. Five serotypes have been isolated, of which AAV-2 is the best characterized. AAV has a single-stranded linear DNA that is encapsidated into capsid proteins VP1, VP2 and VP3 to form an icosahedral virion of 20 to 24 nm in diameter (Muzyczka and McLaughlin, 1988). The AAV DNA is approximately 4.7 kilobases long. It contains two open reading frames and is flanked by two ITRs. There are two major genes in the AAV genome: rep and cap. The rep gene codes for proteins responsible for viral replications, whereas cap codes for capsid protein VPl-3. Each ITR forms a T-shaped hairpin structure. These terminal repeats are the only essential cis components of the AAV for chromosomal integration. Therefore, the AAV can be used as a vector with all viral coding sequences removed and replaced by the cassette of genes for delivery. Three viral promoters have been identified and named p5, pi 9, and p40, according to their map position. Transcription from p5 and pi 9 results in production of rep proteins, and transcription from p40 produces the capsid proteins (Hermonat and Muzyczka, 1984). There are several factors that prompted researchers to study the possibility of using rAAV as an expression vector. One is that the requirements for delivering a gene to integrate into the host chromosome are surprisingly few. It is necessary to have the 145-bp ITRs, which are only 6% of the AAV genome. This leaves room in the vector to assemble a 4.5-kb DNA insertion. While this carrying capacity may prevent the AAV from delivering large genes, it is amply suited for delivering the photoreceptor cell degradation inhibition nucleic acid and antisense constructs of the present invention. AAV is also a good choice of delivery vehicles due to its safety. There is a relatively complicated rescue mechanism: not only wild type adenovirus but also AAV genes are required to mobilize rAAV. Likewise, AAV is not pathogenic and not associated with any disease. The removal of viral coding sequences minimizes immune reactions to viral gene expression, and therefore, rAAV does not evoke an inflammatory response. AAV therefore, represents an ideal candidate for delivery of the present hammerhead ribozyme constructs. Retroviruses have promise as gene delivery vectors due to their ability to integrate their genes into the host genome, transferring a large amount of foreign genetic material, infecting a broad spectrum of species and cell types and of being packaged in special cell-lines. Of course, in using viral delivery systems, one will desire to purify the virion sufficiently to render it essentially free of undesirable contaminants, such as defective interfering viral particles or endotoxins and other pyrogens such that it will not cause any untoward reactions in the cell, animal or individual receiving the vector construct. A preferred means of purifying the vector involves the use of buoyant density gradients, such as cesium chloride gradient centrifugation. V. Secretion Sequences To ensure transit of the degradation-inhibitory protein from the RPE or Muller cell to the photoreceptor cells, the DNA coding sequence may be preceded by a secretory sequence, such as the secretory sequence of immunoglobulin G (IgG), human growth factor (HGF) or IL-7. It is expected that these sequences will allow the secretion of the degradation-inhibitory expression products from the retinal pigment epithelium and Muller cells into the interphotoreceptor matrix (IPM), which would make the products available to the photoreceptor cells. Certain proteins delivered into the IPM by intravitreal injection were found to afford protection of photoreceptor cells (LaVail et al. 1998). Secretion of protective proteins from the RPE or Muller cells into the IPM also reduce photoreceptor degeneration. This approach to genetic treatment extends the time that treatment is effective, relative to gene-based approaches that target photoreceptor cells, because the number of retinal pigment epithelial cells available for transfection does not decrease over the course of retinal disease, whereas photoreceptor cells undergo degeneration and cell death. A 19 amino acid consensus signal sequence peptide, and the nucleic acid sequence encoding the signal sequence, has been reported for the human IgG gamma chain (GenBank accession number A18403). HGF signal sequences have been disclosed in U.S. Patent Nos. 5,606,029 and 5,538,861, incorporated herein by reference. Another exemplary secretory sequence, or signal peptide, is the amino terminal 25 amino acids of the leader sequence of murine interleukin-7 (IL-7; Namen et al, 1988). Other signal peptides may also be employed furthermore, certain nucleotides in the IgG, HGF and IL-7 leader sequence can be altered without altering the amino acid sequence. Additionally, amino acid changes that do not affect the ability of the IgG, HGF and IL-7 sequence to act as a leader sequence can be made. VI. Pharmaceutical Compositions and Routes of Administration In aspects of the invention involving administration of the photoreceptor cell degradation inhibitory compounds to an animal, for example a human subject, the photoreceptor cell degradation inhibitory compounds are preferably dispersed in a pharmaceutically acceptable excipient or solution. The pharmaceutical compositions comprising the photoreceptor cell degradation inhibitory compounds may be administered parenterally, intraperitoneally or topically. Solutions of the active compounds as free base or pharmacologically acceptable salts can be prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. For the treatment of ophthalmic conditions, the photoreceptor cell degradation inhibitory compounds may also be advantageously administered extraocularly or intraocularly, by topical application, inserts, injection, implants, cell therapy or gene therapy. For example, slow-releasing implants containing the photoreceptor cell degradation inhibitory compound embedded in a biodegradable polymer matrix can deliver photoreceptor cell degradation inhibitory compounds. Photoreceptor cell degradation inhibitory compounds may be administered extracerebrally in a form that has been modified chemically or packaged so that it passes the blood-brain barrier, or it may be administered in connection with one or more agents capable of promoting penetration of the photoreceptor cell degradation inhibitory compound across the barrier. Similarly, the photoreceptor cell degradation inhibitory compounds may be administered intraocularly, or it may be administered extraocularly in connection with one or more agents capable of promoting penetration or transport of the photoreceptor cell degradation inhibitory compound across the membranes of the eye. The frequency of dosing will depend on the pharmacokinetic parameters of the photoreceptor cell degradation inhibitory compounds as formulated, and the route of administration. The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin. Sterile injectable solutions are prepared by incorporating the active compounds in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum-drying and freeze-drying techniques which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile- filtered solution thereof. The pharmaceutical compositions disclosed herein may also be orally administered, for example, with an inert diluent or with an assimilable edible carrier, or they may be enclosed in hard or soft shell gelatin capsule, or they may be compressed into tablets, or they may be incorporated directly with the food of the diet. For oral therapeutic administration, the active compounds may be incorporated with excipients and used in the form of ingestible tablets, buccal tables, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. Such compositions and preparations should contain at least 0.1 % of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be between about 2 to about 60% of the weight of the unit. The amount of active compounds in such therapeutically useful compositions is such that a suitable dosage will be obtained. The tablets, troches, pills, capsules and the like may also contain the following: a binder, as gum tragacanth, acacia, cornstarch, or gelatin; excipients, such as dicalcium phosphate; a disintegrating agent, such as corn starch, potato starch, alginic acid and the like; a lubricant, such as magnesium stearate; and a sweetening agent, such as sucrose, lactose or saccharin may be added or a flavoring agent, such as peppermint, oil of wintergreen, or cherry flavoring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier. Various other materials may be present as coatings or to otherwise modify the physical form of the dosage unit. For instance, tablets, pills, or capsules may be coated with shellac, sugar or both. A syrup of elixir may contain the active compounds sucrose as a sweetening agent methyl and propylparabens as preservatives, a dye and flavoring, such as cherry or orange flavor. Of course, any material used in preparing any dosage unit form should be pharmaceutically pure and substantially non-toxic in the amounts employed. In addition, the active compounds may be incoφorated into sustained-release preparation and formulations. As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absoφtion delaying agents and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incoφorated into the compositions. The phrase "pharmaceutically acceptable" refers to molecular entities and compositions that do not produce an allergic or similar untoward reaction when administered to a human. The preparation of an aqueous composition that contains a protein as an active ingredient is well understood in the art. Typically, such compositions are prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid prior to injection can also be prepared. The preparation can also be emulsified. The composition can be formulated in a neutral or salt form. Pharmaceutically acceptable salts, include the acid addition salts (formed with the free amino groups of the protein) and which are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, oxalic, tartaric, mandelic, and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium, or ferric hydroxides, and such organic bases as isopropylamine, trimethylamine, histidine, procaine and the like. Upon formulation, solutions will be administered in a manner compatible with the dosage formulation and in such amount as is therapeutically effective. The formulations are easily administered in a variety of dosage forms such as injectable solutions, drug release capsules and the like. For parenteral administration in an aqueous solution, for example, the solution should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. These particular aqueous solutions are especially suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. In this connection, sterile aqueous media that can be employed will be known to those of skill in the art in light of the present disclosure. For example, one dosage could be dissolved in 1 ml of isotonic NaCl solution and either added to 1000 ml of hypodermoclysis fluid or injected at the proposed site of infusion, (see for example, "Remington's Pharmaceutical Sciences" 15th Edition, pages 1035-1038 and 1570-1580). Some variation in dosage will necessarily occur depending on the condition of the subject being treated. The person responsible for administration will, in any event, determine the appropriate dose for the individual subject. Moreover, for human administration, preparations should meet sterility, pyrogenicity, general safety and purity standards as required by FDA Office of Biologies standards. VII. Liposomes and Nanocapsules In certain embodiments, the inventors contemplate the use of liposomes and/or nanocapsules for the introduction of particular peptides or nucleic acid segments into host cells. Such formulations may be preferred for the introduction of pharmaceutically-acceptable formulations of the nucleic acids, peptides, and/or antibodies disclosed herein. The formation and use of liposomes is generally known to those of skill in the art (see for example, Couvreur et al, 1977, which describes the use of liposomes and nanocapsules in the targeted antibiotic therapy of intracellular bacterial infections and diseases). Recently, liposomes were developed with improved serum stability and circulation half-times (Gabizon and Papahadjopoulos, 1988; Allen and Choun, 1987). Nanocapsules can generally entrap compounds in a stable and reproducible way (Henry-Michelland et al, 1987). To avoid side effects due to intracellular polymeric overloading, such ultrafine particles (sized around 0.1 μm) should be designed using polymers able to be degraded in vivo. Biodegradable polyalkyl- cyanoacrylate nanoparticles (Couvreur et al, 1977; 1988), which meet these requirements, are contemplated for use in the present invention. Liposomes are formed from phospholipids that are dispersed in an aqueous medium and spontaneously form multilamellar concentric bilayer vesicles (also termed multilamellar vesicles (MLVs). MLVs generally have diameters of from 25 nm to 4 μm. Sonication of MLVs results in the formation of small unilamellar vesicles (SUVs) with diameters in the range of 200 to 500 A, containing an aqueous solution in the core. In addition to the teachings of Couvreur et al. (1988), the following information may be utilized in generating liposomal formulations. Phospholipids can form a variety of structures other than liposomes when dispersed in water, depending on the molar ratio of lipid to water. At low ratios the liposome is the preferred structure. The physical characteristics of liposomes depend on pH, ionic strength and the presence of divalent cations. Liposomes can show low permeability to ionic and polar substances, but at elevated temperatures undergo a phase transition that markedly alters their permeability. The phase transition involves a change from a closely packed, ordered structure, known as the gel state, to a loosely packed, less- ordered structure, known as the fluid state. This occurs at a characteristic phase- transition temperature and results in an increase in permeability to ions, sugars and drugs. Liposomes interact with cells via four different mechanisms: endocytosis by phagocytic cells of the reticuloendothelial system such as macrophages and neutrophils; adsoφtion to the cell surface, either by nonspecific weak hydrophobic or electrostatic forces, or by specific interactions with cell-surface components; fusion with the plasma cell membrane by insertion of the lipid bilayer of the liposome into the plasma membrane, with simultaneous release of liposomal contents into the cytoplasm; and by transfer of liposomal lipids to cellular or subcellular membranes, or vice versa, without any association of the liposome contents. It often is difficult to determine which mechanism is operative and more than one may operate at the same time. VIII. Therapeutic Kits Therapeutic kits comprising, in a suitable container, at least a first, or at least a first and a second genetic construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor cell degradation-inhibitory agent in a pharmaceutically acceptable formulation represent another aspect of the invention. The photoreceptor cell degradation-inhibitory compositions may be native photoreceptor cell degradation- inhibitory proteins, truncated photoreceptor cell degradation-inhibitory proteins, site- specifically mutated photoreceptor cell degradation-inhibitory proteins, or photoreceptor cell degradation-inhibitory protein-encoded peptide epitopes. In other embodiments, the photoreceptor cell degradation-inhibitory protein compositions may be nucleic acid segments encoding native photoreceptor cell degradation-inhibitory proteins, truncated photoreceptor cell degradation-inhibitory proteins, site-specifically mutated photoreceptor cell degradation-inhibitory proteins, or photoreceptor cell degradation-inhibitory protein-encoded peptide epitopes. Such nucleic acid segments may be DNA or RNA, and may be either native, recombinant, or mutagenized nucleic acid segments. Kits comprising at least a first genetic construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor cell degradation-inhibitory agent in a pharmaceutically acceptable formulation, and at least a first distinct ophthalmic therapeutic agent are also provided. The kits may comprise a single container that contains the photoreceptor cell degradation-inhibitory compositions. The container may, if desired, contain a pharmaceutically acceptable sterile excipient, having associated with it the photoreceptor cell degradation-inhibitory compositions. The formulation may be in the form of a gelatinous composition, e.g., a collagenous-photoreceptor cell degradation-inhibitory composition, or may even be in a more fluid form that nonetheless forms a gel-like composition upon administration to the body. In these cases, the container means may itself be a syringe, pipette, or other such like apparatus, from which the photoreceptor cell degradation-inhibitory composition may be applied to a tissue site, for example ocularly. However, the single container means may contain a dry, or lyophilized, mixture of a photoreceptor cell degradation- inhibitory composition, which may or may not require pre-wetting before use. Alternatively, the kits of the invention may comprise a distinct container for each component. In such cases, separate or distinct containers would contain the photoreceptor cell degradation-inhibitory compositions, either as a sterile DNA solution or in a lyophilized form. The kits may also comprise a third container for containing a sterile, pharmaceutically acceptable buffer, diluent or solvent. Such a solution may be required to formulate the photoreceptor cell degradation-inhibitory components into a more suitable form for application to the body, e.g., as a topical preparation, or alternatively, in oral, parenteral, or intravenous forms. It should be noted, however, that all components of a kit could be supplied in a dry form (lyophilized), which would allow for "wetting" upon contact with body fluids. Thus, the presence of any type of pharmaceutically acceptable buffer or solvent is not a requirement for the kits of the invention. The container(s) will generally be a container such as a vial, test tube, flask, bottle, syringe or other container, into which the components of the kit may placed. The photoreceptor cell degradation-inhibitory compositions may also be aliquoted into smaller containers, should this be desired. The kits of the present invention may also include material for containing the individual containers in close confinement for commercial sale, such as, e.g., injection or blow-molded plastic containers into which the desired vials or syringes are retained. Irrespective of the number of containers, the kits of the invention may also comprise, or be packaged with, an instrument for assisting with the placement of the photoreceptor cell degradation-inhibitory compositions within the eye or the body of an animal. Such an instrument may be a syringe, pipette, forceps, or any such medically approved delivery vehicle. IX. Biological Functional Equivalents Modification and changes may be made in the structure of the proteins and/or peptides of the present invention, and DNA segments that encode them, and still obtain a functional molecule that encodes a protein or peptide with desirable characteristics. The following is a discussion based upon changing the amino acids of a protein to create an equivalent, or even an improved, second-generation molecule. The amino acid changes may be achieved by changing the codons of the DNA sequence, according to Table 2. Table 2 Amino Acids Codons Alanine Ala A GCA GCC GCG GCU Cysteine Cys C UGC UGU Aspartic acid Asp D GAC GAU Glutamic acid Glu E GAA GAG Phenylalanine Phe F UUC uuu Glycine Gly G GGA GGC GGG GGU Histidine His H CAC CAU Isoleucine He I AUA AUC AUU Lysine Lys K AAA AAG Leucine Leu L UUA UUG CUA CUC CUG CUU Methionine Met M AUG Asparagine Asn N AAC AAU Proline Pro P CCA CCC CCG CCU Glutamine Gin Q CAA CAG Arginine Arg R AGA AGG CGA CGC CGG CGU Serine Ser S AGC AGU UCA UCC UCG UCU Threonine Thr T ACA ACC ACG ACU Valine Val V GUA GUC GUG GUU Tryptophan Tφ w UGG Tyrosine Tyr Y UAC UAU For example, certain amino acids may be substituted for other amino acids in a protein structure without appreciable loss of interactive binding capacity with structures such as, for example, antigen-binding regions of antibodies or binding sites on substrate molecules. Since it is the interactive capacity and nature of a protein that defines that protein's biological functional activity, certain amino acid sequence substitutions can be made in a protein sequence, and, of course, its underlying DNA coding sequence, and nevertheless obtain a protein with like properties. It is thus contemplated by the inventors that various changes may be made in the peptide sequences of the disclosed compositions, or corresponding DNA sequences which encode said proteins and peptides without appreciable loss of their biological utility or activity. In making such changes, the hydropathic index of amino acids may be considered. The importance of the hydropathic amino acid index in conferring interactive biologic function on a protein is generally understood in the art (Kyte and Doolittle, 1982, incoφorated herein by reference). It is accepted that the relative hydropathic character of the amino acid contributes to the secondary structure of the resultant protein, which in turn defines the interaction of the protein with other molecules, for example, enzymes, substrates, receptors, DNA, antibodies, antigens, and the like. Each amino acid has been assigned a hydropathic index on the basis of their hydrophobicity and charge characteristics (Kyte and Doolittle, 1982), these are: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine/cystine (+2.5); methionine (+1.9); alanine (+1.8); glycine (-0.4); threonine (-0.7); serine (- 0.8); tryptophan (-0.9); tyrosine (-1.3); proline (-1.6); histidine (-3.2); glutamate (- 3.5); glutamine (-3.5); aspartate (-3.5); asparagine (-3.5); lysine (-3.9); and arginine (- 4.5). It is known in the art that certain amino acids may be substituted by other amino acids having a similar hydropathic index or score and still result in a protein with similar biological activity, i.e., still obtain a biological functionally equivalent protein. In making such changes, the substitution of amino acids whose hydropathic indices are within ±2 is preferred, those that are within ±1 are particularly preferred, and those within ±0.5 are even more particularly preferred. It is also understood in the art that the substitution of like amino acids can be made effectively on the basis of hydrophilicity. U.S. Patent 4,554,101, incoφorated herein by reference, states that the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with a biological property of the protein. As detailed in U.S. Patent 4,554,101, the following hydrophilicity values have been assigned to amino acid residues: arginine (+3.0); lysine (+3.0); aspartate (+3.0 ± 1); glutamate (+3.0 ± 1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine (0); threonine (-0.4); proline (-0.5 ± 1); alanine (-0.5); histidine (-0.5); cysteine (-1.0); methionine (-1.3); valine (-1.5); leucine (-1.8); isoleucine (-1.8); tyrosine (-2.3); phenylalanine (-2.5); tryptophan (-3.4). It is understood that an amino acid can be substituted for another having a similar hydrophilicity value and still obtain a biologically equivalent, and in particular, an immunologically equivalent protein. In such changes, the substitution of amino acids whose hydrophilicity values are within ±2 is preferred, those that are within ±1 are particularly preferred, and those within ±0.5 are even more particularly preferred. As outlined above, amino acid substitutions are generally therefore based on the relative similarity of the amino acid side-chain substituents, for example, their hydrophobicity, hydrophilicity, charge, size, and the like. Exemplary substitutions which take various of the foregoing characteristics into consideration are well known to those of skill in the art and include: arginine and lysine; glutamate and aspartate; serine and threonine; glutamine and asparagine; and valine, leucine and isoleucine. X. Site-Specific Mutagenesis Site-specific mutagenesis is a technique useful in the preparation of individual proteins or peptides, or biologically functional equivalent proteins or peptides, through specific mutagenesis of the underlying DNA. The technique, well-known to those of skill in the art, further provides a ready ability to prepare and test sequence variants, for example, incoφorating one or more of the foregoing considerations, by introducing one or more nucleotide sequence changes into the DNA. Site-specific mutagenesis allows the production of mutants through the use of specific oligonucleotide sequences which encode the DNA sequence of the desired mutation, as well as a sufficient number of adjacent nucleotides, to provide a primer sequence of sufficient size and sequence complexity to form a stable duplex on both sides of the deletion junction being traversed. Typically, a primer of about 14 to about 25 nucleotides in length is preferred, with about 5 to about 10 residues on both sides of the junction of the sequence being altered. In general, the technique of site-specific mutagenesis is well known in the art, as exemplified by various publications. As will be appreciated, the technique typically employs a phage vector that exists in both a single stranded and double stranded form. Typical vectors useful in site-directed mutagenesis include vectors such as the Ml 3 phage. These phage are readily commercially-available and their use is generally well-known to those skilled in the art. Double-stranded plasmids are also routinely employed in site directed mutagenesis that eliminates the step of transferring the gene of interest from a plasmid to a phage. In general, site-directed mutagenesis in accordance herewith is performed by first obtaining a single-stranded vector or melting apart of two strands of a double-stranded vector that includes within its sequence a DNA sequence that encodes the desired peptide. An oligonucleotide primer bearing the desired mutated sequence is prepared, generally synthetically. This primer is then annealed with the single- stranded vector, and subjected to DNA polymerizing enzymes such as E. coli polymerase I Klenow fragment, in order to complete the synthesis of the mutation- bearing strand. Thus, a heteroduplex is formed wherein one strand encodes the original non-mutated sequence and the second strand bears the desired mutation. This heteroduplex vector is then used to transform appropriate cells, such as E. coli cells, and clones are selected which include recombinant vectors bearing the mutated sequence arrangement. The preparation of sequence variants of the selected peptide-encoding DNA segments using site-directed mutagenesis is provided as a means of producing potentially useful species and is not meant to be limiting as there are other ways in which sequence variants of peptides and the DNA sequences encoding them may be obtained. For example, recombinant vectors encoding the desired peptide sequence may be treated with mutagenic agents, such as hydroxylamine, to obtain sequence variants. Specific details regarding these methods and protocols are found in the teachings of Maloy et al, 1994; Segal, 1976; Prokop and Bajpai, 1991; Kuby, 1994; and Maniatis et al, 1982, each incoφorated herein by reference, for that puφose. The PCR™-based strand overlap extension (SOE) (Ho et al, 1989) for site- directed mutagenesis is particularly preferred for site-directed mutagenesis of the nucleic acid compositions of the present invention. The techniques of PCR™ are well-known to those of skill in the art, as described herein. The SOE procedure involves a two-step PCR™ protocol, in which a complementary pair of internal primers (B and C) are used to introduce the appropriate nucleotide changes into the wild-type sequence. In two separate reactions, flanking PCR™ primer A (restriction site incoφorated into the oligo) and primer D (restriction site incoφorated into the oligo) are used in conjunction with primers B and C, respectively to generate PCR™ products AB and CD. The PCR™ products are purified by agarose gel electrophoresis and the two overlapping PCR™ fragments AB and CD are combined with flanking primers A and D and used in a second PCR™ reaction. The amplified PCR™ product is agarose gel purified, digested with the appropriate enzymes, ligated into an expression vector, and transformed into E. coli JM101, XL 1 -Blue™ (Stratagene, LaJolla, CA), JM105, or TGI (Carter et al, 1985) cells. Clones are isolated and the mutations are confirmed by sequencing of the isolated plasmids. XI. Nucleic Acid Amplification Nucleic acid used as a template for amplification is isolated from cells, according to standard methodologies (Sambrook et al, 1989). The nucleic acid may be genomic DNA or fractionated or whole cell RNA. Where RNA is used, it may be desired to convert the RNA to a complementary DNA. In one embodiment, the RNA is whole cell RNA and is used directly as the template for amplification. Pairs of primers that selectively hybridize to nucleic acids corresponding to the ribozymes or conserved flanking regions are contacted with the isolated nucleic acid under conditions that permit selective hybridization. The term "primer", as defined herein, is meant to encompass any nucleic acid that is capable of priming the synthesis of a nascent nucleic acid in a template-dependent process. Typically, primers are oligonucleotides from ten to twenty base pairs in length, but longer sequences can be employed. Primers may be provided in double-stranded or single-stranded form, although the single-stranded form is preferred. Once hybridized, the nucleic acid:primer complex is contacted with one or more enzymes that facilitate template-dependent nucleic acid synthesis. Multiple rounds of amplification, also referred to as "cycles," are conducted until a sufficient amount of amplification product is produced. Next, the amplification product is detected. In certain applications, the detection may be performed by visual means. Alternatively, the detection may involve indirect identification of the product via chemiluminescence, radioactive scintigraphy of incoφorated radiolabel or fluorescent label or even via a system using electrical or thermal impulse signals (Affymax technology). A number of template dependent processes are available to amplify the marker sequences present in a given template sample. One of the best known amplification methods is the polymerase chain reaction (referred to as PCR™) which is described in detail in U.S. Patent Nos. 4,683,195, 4,683,202 and 4,800,159, and each incoφorated herein by reference in entirety. Briefly, in PCR™, two primer sequences are prepared that are complementary to regions on opposite complementary strands of the marker sequence. An excess of deoxynucleoside triphosphates is added to a reaction mixture along with a DNA polymerase, e.g., Taq polymerase. If the marker sequence is present in a sample, the primers will bind to the marker and the polymerase will cause the primers to be extended along the marker sequence by adding on nucleotides. By raising and lowering the temperature of the reaction mixture, the extended primers will dissociate from the marker to form reaction products, excess primers will bind to the marker and to the reaction products and the process is repeated. A reverse transcriptase PCR amplification procedure may be performed in order to quantify the amount of mRNA amplified. Methods of reverse transcribing RNA into cDNA are well known and described in Sambrook et al, 1989. Alternative methods for reverse transcription utilize thermostable, RNA-dependent DNA polymerases. These methods are described in WO 90/07641, filed December 21, 1990, incoφorated herein by reference. Polymerase chain reaction methodologies are well known in the art. Another method for amplification is the ligase chain reaction ("LCR"), disclosed in EPA No. 320 308, incoφorated herein by reference in its entirety. In LCR, two complementary probe pairs are prepared, and in the presence of the target sequence, each pair will bind to opposite complementary strands of the target such that they abut. In the presence of a ligase, the two probe pairs will link to form a single unit. By temperature cycling, as in PCR, bound ligated units dissociate from the target and then serve as "target sequences" for ligation of excess probe pairs. U.S. Patent 4,883,750 describes a method similar to LCR for binding probe pairs to a target sequence. Qbeta Replicase, described in PCT Application No. PCT/US87/00880, incoφorated herein by reference, may also be used as still another amplification method in the present invention. In this method, a replicative sequence of RNA that has a region complementary to that of a target is added to a sample in the presence of an RNA polymerase. The polymerase will copy the replicative sequence that can then be detected. An isothermal amplification method, in which restriction endonucleases and ligases are used to achieve the amplification of target molecules that contain nucleotide 5'-[alpha-thio]-triphosphates in one strand of a restriction site may also be useful in the amplification of nucleic acids in the present invention. Strand Displacement Amplification (SDA), described in U. S. Patent Nos. 5,455,166, 5,648,211, 5,712,124 and 5,744,311, each incoφorated herein by reference, is another method of carrying out isothermal amplification of nucleic acids which involves multiple rounds of strand displacement and synthesis, i.e., nick translation. A similar method, called Repair Chain Reaction (RCR), involves annealing several probes throughout a region targeted for amplification, followed by a repair reaction in which only two of the four bases are present. The other two bases can be added as biotinylated derivatives for easy detection. A similar approach is used in SDA. Target specific sequences can also be detected using a cyclic probe reaction (CPR). In CPR, a probe having 3' and 5' sequences of non-specific DNA and a middle sequence of specific RNA is hybridized to DNA that is present in a sample. Upon hybridization, the reaction is treated with RNase H, and the products of the probe identified as distinctive products that are released after digestion. The original template is annealed to another cycling probe and the reaction is repeated. Still another amplification methods described in GB Application No. 2 202 328, and in PCT Application No. PCT/US89/01025, each of which is incoφorated herein by reference in its entirety, may be used in accordance with the present invention. In the former application, "modified" primers are used in a PCR-like, template- and enzyme-dependent synthesis. The primers may be modified by labeling with a capture moiety (e.g., biotin) and/or a detector moiety (e.g., enzyme). In the latter application, an excess of labeled probes is added to a sample. In the presence of the target sequence, the probe binds and is cleaved catalytically. After cleavage, the target sequence is released intact to be bound by excess probe. Cleavage of the labeled probe signals the presence of the target sequence. Other nucleic acid amplification procedures include transcription-based amplification systems (TAS), including nucleic acid sequence based amplification (NASBA) and 3SR Gingeras et al, PCT Application WO 88/10315, incoφorated herein by reference. In NASBA, the nucleic acids can be prepared for amplification by standard phenol/chloroform extraction, heat denaturation of a clinical sample, treatment with lysis buffer and minispin columns for isolation of DNA and RNA or guanidinium chloride extraction of RNA. These amplification techniques involve annealing a primer that has target specific sequences. Following polymerization, DNA/RNA hybrids are digested with RNase H while double stranded DNA molecules are heat denatured again. In either case the single stranded DNA is made fully double stranded by addition of second target specific primer, followed by polymerization. The double-stranded DNA molecules are then multiply transcribed by an RNA polymerase such as T7 or SP6. In an isothermal cyclic reaction, the RNA's are reverse transcribed into single stranded DNA, which is then converted to double stranded DNA, and then transcribed once again with an RNA polymerase such as T7 or SP6. The resulting products, whether truncated or complete, indicate target specific sequences. Davey et al, EPA No. 329 822 (incoφorated herein by reference in its entirety) disclose a nucleic acid amplification process involving cyclically synthesizing single-stranded RNA ("ssRNA"), ssDNA, and double-stranded DNA (dsDNA), which may be used in accordance with the present invention. The ssRNA is a template for a first primer oligonucleotide, which is elongated by reverse transcriptase (RNA-dependent DNA polymerase). The RNA is then removed from the resulting DNA:RNA duplex by the action of ribonuclease H (RNase H, an RNase specific for RNA in duplex with either DNA or RNA). The resultant ssDNA is a template for a second primer, which also includes the sequences of an RNA polymerase promoter (exemplified by T7 RNA polymerase) 5' to its homology to the template. This primer is then extended by DNA polymerase (exemplified by the large "Klenow" fragment of E. coli DNA polymerase I), resulting in a double-stranded DNA ("dsDNA") molecule, having a sequence identical to that of the original RNA between the primers and having additionally, at one end, a promoter sequence. This promoter sequence can be used by the appropriate RNA polymerase to make many RNA copies of the DNA. These copies can then re-enter the cycle leading to very swift amplification. With proper choice of enzymes, this amplification can be done isothermally without addition of enzymes at each cycle. Because of the cyclical nature of this process, the starting sequence can be chosen to be in the form of either DNA or RNA. Miller et al, PCT Application WO 89/06700 (incoφorated herein by reference in its entirety) disclose a nucleic acid sequence amplification scheme based on the hybridization of a promoter/primer sequence to a target single-stranded DNA ("ssDNA") followed by transcription of many RNA copies of the sequence. This scheme is not cyclic, i.e., new templates are not produced from the resultant RNA transcripts. Other amplification methods include "RACE" and "one-sided PCR" (Frohman, 1990 incoφorated by reference). Methods based on ligation of two (or more) oligonucleotides in the presence of nucleic acid having the sequence of the resulting "di-oligonucleotide", thereby amplifying the di-oligonucleotide, may also be used in the amplification step of the present invention. Following any amplification, it may be desirable to separate the amplification product from the template and the excess primer for the puφose of determining whether specific amplification has occurred. In one embodiment, amplification products are separated by agarose, agarose-acrylamide or polyacrylamide gel electrophoresis using standard methods (Sambrook et al, 1989). Alternatively, chromatographic techniques may be employed to effect separation. There are many kinds of chromatography which may be used in the present invention: adsoφtion, partition, ion-exchange and molecular sieve, and many specialized techniques for using them including column, paper, thin-layer and gas chromatography. Amplification products must be visualized in order to confirm amplification of the marker sequences. One typical visualization method involves staining of a gel with ethidium bromide and visualization under UV light. Alternatively, if the amplification products are integrally labeled with radio- or fluorometricalfy-labeled nucleotides, the amplification products can then be exposed to x-ray film or visualized under the appropriate stimulating spectra, following separation. In one embodiment, visualization is achieved indirectly. Following separation of amplification products, a labeled, nucleic acid probe is brought into contact with the amplified marker sequence. The probe preferably is conjugated to a chromophore but may be radiolabeled. In another embodiment, the probe is conjugated to a binding partner, such as an antibody or biotin, and the other member of the binding pair carries a detectable moiety. In one embodiment, detection is by Southern blotting and hybridization with a labeled probe. The techniques involved in Southern blotting are well known to those of skill in the art and can be found in many standard books on molecular protocols (Sambrook et al, 1989). Briefly, amplification products are separated by gel electrophoresis. The gel is then contacted with a membrane, such as nitrocellulose, permitting transfer of the nucleic acid and non-covalent binding. Subsequently, the membrane is incubated with a chromophore-conjugated probe that is capable of hybridizing with a target amplification product. Detection is by exposure of the membrane to x-ray film or ion-emitting detection devices. One example of the foregoing is described in U.S. Patent No. 5,279,721, incoφorated by reference herein, which discloses an apparatus and method for the automated electrophoresis and transfer of nucleic acids. The apparatus permits electrophoresis and blotting without external manipulation of the gel and is ideally suited to carrying out methods according to the present invention. The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered by the inventors to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments that are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention. EXAMPLE 1 Cloning of RPE-Specific Promoter Sequences To assess the ability of putative RPE cell- and Muller cell-specific promoters to promote expression of a DNA sequence in RPE and Muller cells, upstream regions from three genes specific for RPE and Muller cells were cloned into the pTR-UF5 vector (Flannery et al. 1997) using standard molecular biology techniques known to one of skill in the art. Upstream regions from the following three genes were employed: (1) cellular retinaldehyde-binding protein (CRALBP) (Intres et al, 1994; Kennedy et al, 1998); (2) 11-cis retinol dehydrogenase (11-cis RDH) (Driessen et al, 1995; Simon et al, 1995; Simon et al, 1996) and (3) RPE65 (Nicoletti et al, 1998). The upstream sequence for CRALBP, RPE65 and 11-cis RDH were obtained from Genbank (Accession Numbers L34219, U20510 and X97752, respectively). Recent studies have indicated the optimal length of the CRALBP and RPE65 promoter regions for transient expression of reporter genes in RPE cell lines is 2.1 kb (Kennedy et al, 1998) and 1.3 kb (Nicoletti et al, 1998), respectively. The optimal length of the 11-cis RDH promoter has yet to be determined. 5' 11-cis RDH sequences of approximately 0.5, 1.0 and 3.0 kb were studied for the ability to promote expression of reporter genes in RPE cell lines. The results reported here were obtained with a 528 bp promoter. Promoter regions of 1.0 and 3.0 kb are in the process of being tested. The upstream regions of CRALBP and RPE65 were amplified from genomic human DNA by polymerase chain reaction using suitable oligonucleotides primer pairs and standard reaction conditions. The sequences of primers used to amplify CRALBP are provided in SEQ ID NO:4 and SEQ ID NO:5; sequences of primers used to amplify RPE65 are shown in SEQ ID NO: 6 and SEQ ID NO:7. The promoter region of 11-cis RDH was amplified from cloned murine DNA. The pTR-UF5 vector contains a cytomegalovirus (CMV) promoter cloned into Kpnl/Xbαl sites of the vector. The CMV promoter of the pTR-UF5 vector was replaced by SEQ ID NO:l, SEQ ID NO:2, or SEQ ID NO:3 to create plasmids containing each promoter capable of expression of the marker gene. These constructs contain the GFP reporter gene (Zolutkhin et αl, 1996; Flannery et αl, 1997) downstream from the test promoter sequences. EXAMPLE 2 Expression of GFP Reporter Gene in RPE Cells The plasmids were packaged into rAAV virus particles as described previously (Ferrari et αl. 1997; Flannery et αl. 1997). The rAAV virus batches were titered and found to have a titer of at least 1 x 10 12 virus particles per ml. Two-μl aliquots of the virus suspensions were injected into the subretinal spaces of adult rats. Five weeks post injection, GFP expression was visualized in retinal cross sections using a fluorescence microscope equipped with filters for FITC fluorescence. GFP expression, which manifested as a green band located between the outer segment layer of the retina and the choroid, coincided with the exact location of RPE cells. Each construct resulted in RPE-specific expression of GFP. No cells other than RPE cells were found to express GFP. At or near the site of injection, the efficiency of transfection was approximately 100%. In the adult rat, the region surrounding the injection site encompasses approximately 35%) of the total retinal area. The 2-μl virus suspension transduced approximately 35% of the RPE and Muller cells, and hence could deliver therapeutic agents to at least 35% of the rod and cone photoreceptor population. The En-face analysis of whole-mount eyecup preparations in a confocal microscope displayed expression of GFP within typical hexagonal shapes of RPE cells. These results indicate that the promoter constructs of CRALBP, RPE65, and 11-cis RDH cloned into the pTR-UF5 vectors were sufficient for RPE-specific expression of the reporter gene. These promoters can drive RPE-specific expression of degradation-inhibitory genes. One candidate for treating retinal disease using gene therapy is ciliary neurotrophic factor, a potent inhibitor of the apoplectic suicide pathway in neuronal cells, including photoreceptor cells. By delivering copies of the CNTF gene placed under the control of an RPE- or Muller cell-specific promoter to RPE or Muller cells, reduced or delayed degeneration of photoreceptor cells associated with conditions such as diabetes or retinopathy of prematurity can be achieved. All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods, and in the steps or in the sequence of steps of the methods described herein, without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents that are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims. 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Claims: WHAT IS CLAIMED IS: 1. A DNA construct comprising a retinal pigment epithelial cell- or Muller cell- specific promoter operably linked to a first DNA sequence that encodes a photoreceptor degradation-inhibitory agent. 2. The DNA construct of claim 1, wherein the promoter is a retinal pigment epithelial cell-specific promoter. 3. The DNA construct of claim 1, wherein the promoter is a Muller cell-specific promoter. 4. The DNA construct of claim 1, wherein the promoter is a cellular retinaldehyde-binding protein gene, an 11-cis retinol dehydrogenase gene or a RPE 65 gene promoter. 5. The DNA construct of claim 4, wherein the promoter is an 11-cis retinol dehydrogenase gene promoter. 6. The DNA construct of claim 5, wherein the promoter has the sequence from between about nucleotide 1 to about nucleotide 528 of SEQ ID NO: 1. 7. The DNA construct of claim 5, wherein the promoter has the sequence of SEQ ID NO: l. 8. The DNA construct of claim 4, wherein the promoter is a cellular retinaldehyde-binding protein gene promoter. 9. The DNA construct of claim 8, wherein the promoter has the sequence of SEQ ID NO: 2. 10. The DNA construct of claim 4, wherein the promoter is an RPE 65 gene promoter. 11. The DNA construct of claim 10, wherein the promoter has the sequence of SEQ ID NO: 3. 12. The DNA construct of claim 1, wherein the DNA sequence encodes a photoreceptor degradation-inhibitory protein. 13. The DNA construct of claim 12, wherein the photoreceptor degradation- inhibitory protein is a ciliary neurotrophic factor. 14. The DNA construct of claim 12, wherein the photoreceptor degradation- inhibitory protein is a brain derived neurotrophic factor. 15. The DNA construct of claim 12, wherein the photoreceptor degradation- inhibitory protein is a fibroblast growth factor. 16. The DNA construct of claim 1, wherein the DNA construct comprises a second DNA sequence that encodes a secretory peptide, wherein the secretory sequence and the DNA sequence are linked as a single transcriptional unit that encodes a fusion protein comprising said secretory peptide linked to said photoreceptor degradation-inhibitory agent. 17. The DNA construct of claim 16, wherein the DNA construct comprises a second DNA sequences that encodes an immunoglobulin G secretory peptide. 18. The DNA construct of claim 16, wherein the DNA construct comprises a second DNA sequence that encodes a human growth factor secretory peptide. 19. The DNA construct of claim 1 , comprised within a recombinant vector. 20. The DNA construct of claim 19, comprised within a recombinant viral vector. 21. The DNA construct of claim 20, comprised within a recombinant adeno- associated viral vector. 22. The DNA construct of claim 20, comprised within a recombinant virus. 23. The DNA construct of claim 22, comprised within a recombinant adeno- associated virus. 24. The DNA construct of any previous claim, dispersed in a pharmaceutically acceptable excipient. 25. A pharmaceutical composition comprising a DNA construct in accordance with any previous claim. 26. A recombinant vector comprising a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation-inhibitory agent. 27. The recombinant vector of claim 26, wherein said recombinant vector is a recombinant viral vector. 28. The recombinant vector of claim 27, wherein said recombinant viral vector is a recombinant adeno-associated viral vector. 29. A recombinant virus comprising a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation-inhibitory agent. 30. The recombinant virus of claim 29, wherein said recombinant virus is a recombinant adeno-associated virus. 31. A recombinant adeno-associated virus comprising a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation-inhibitory agent. 32. A DNA construct, vector or virus in accordance with any preceding claim, for use in treating or preventing retinal cell photoreceptor apoptosis or necrosis. 33. The DNA construct of claim 32, wherein the retinal cell photoreceptor apoptosis or necrosis is associated with retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, optic neuritis or retinopathy of prematurity. 34. Use of a DNA construct or virus in accordance with any preceding claim, in the manufacture of a medicament for treating or preventing retinal cell photoreceptor apoptosis or necrosis. 35. Use in accordance with claim 34, wherein the medicament is intended for treating or preventing retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy or retinopathy of prematurity. 36. A kit comprising, in a suitable container, a DNA construct in accordance with any one of claims 1 through 24. 37. The kit of claim 36, comprising a second, distinct ophthalmic therapeutic composition. 38. A method for inhibiting apoptosis or necrosis in retinal photoreceptor cells, comprising contacting retinal pigment epithelial or Muller cells with a DNA construct comprising a retinal pigment epithelial cell- or Muller cell-specific promoter operably linked to a DNA sequence that encodes a photoreceptor degradation-inhibitory agent. 39. The method of claim 38, wherein said DNA construct is comprised within a viral vector, said viral vector administered to said retinal pigment epithelial or Muller cells. 40. The method of claim 39, wherein said DNA construct is comprised within an adeno-associated viral vector, said adeno-associated viral vector administered to said retinal pigment epithelial or Muller cells. 41. The method of claim 38, wherein the retinal pigment epithelial or Muller cells are comprised within an animal. 42. The method of claim 41, wherein the retinal pigment epithelial or Muller cells are comprised within a human subject. 43. The method of claim 38, wherein the retinal photoreceptor cell apoptosis or necrosis is associated with retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, optic neuritis or retinopathy of prematurity.

Inventors: HAUSWIRTH WILLIAM W, JANSSEN JACQUES J, TIMMERS ADRIAN M, HAUSWIRTH, WILLIAM, W., JANSSEN, JACQUES, J., TIMMERS, ADRIAN, M.
Applicants: CATHOLIC UNIVERSITY NIJMEGEN, HAUSWIRTH WILLIAM W, JANSSEN JACQUES J, TIMMERS ADRIAN M, UNIV FLORIDA, HAUSWIRTH, WILLIAM, W., JANSSEN, JACQUES, J., TIMMERS, ADRIAN, M., UNIVERSITY OF FLORIDA
Application year: 1999
Main classification: C12N15
IPC codes: A61K38, A61K48, A61P27, C07K14, C12N9, C12N15