bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of High-Dose Corticosteroid Therapy on Optic Nerve Head Blood Flow in Experimental Traumatic Optic Neuropathy
Authors: Lew Helen , Lee Sang Yeul , Jang Jae Woo , Kim Hye Young , Kang Shin Jeong , Kim Sung Joo
Published: April 2003

Purpose: The objective of this study was to ascertain the effect of high-dose steroid therapy in traumatic optic neuropathy using the Heidelberg retina flowmeter (HRF) to detect changes in optic nerve head blood flow. Methods: We experimentally damaged the optic nerves of 10 white rabbits with a Hartman mosquito clamp. The first group (n = 5) was treated with intravenous dexamethasone (0.25 mg/kg) every 6 h for a 48-hour period. The second group (n = 5) served as controls. Both groups were tested prior to operation, 1 week, 1 month and 2 months after surgery. Results: Experimental optic nerve damage caused a significant decrease in optic nerve head blood flow of 50.51% (p = 0.001), with a volume decrease of 46.02% (p = 0.001) and a velocity reduction of 43.12% (p = 0.002) compared to the baseline. After 2 months, in the group treated with high-dose corticosteroid therapy, optic nerve head blood flow was increased by 76.90% (p = 0.012), volume by 77.53% (p = 0.012) and velocity by 47.21% (p = 0.012) compared to the control group. Conclusion: The high-dose corticosteroid therapy improved the optic nerve head blood flow as demonstrated in experimental traumatic optic neuropathy. The HRF may be used to assess the therapeutic responses in traumatic optic neuropathy under variable conditions.
Combined Pharmacologic Therapy in a Rabbit Model of Proliferative Vitreoretinopathy (PVR)
Authors: Pastor J. Carlos , Rodríguez Elena , Marcos Manuel A. , Lopez M.I.
Published: April 2003

Purpose: This study was designed to evaluate the efficacy of a combined treatment, previously used to prevent fibrosis after glaucoma surgery, to inhibit an experimental model of proliferative vitreoretinopathy (PVR). Methods: Two groups of albino rabbits were used. In the control group (group 1, n = 14), experimental PVR was induced using vitrectomy, retinotomies, cryotherapy and intraocular injection of platelet-rich plasma. In the experimental group (group 2, n = 15), after PVR was induced, the following treatment was administered for 4 weeks: systemic methylprednisolone, sodium diclofenac and colchicine combined with topical atropine 1%, adrenaline 10% and dexamethasone phosphate 0.1%. Follow- up consisted of fundus examination for 4 weeks. Results were classified according to Fastenberg’s classification. Only retinal detachments were considered to compare the two groups. Nonparametric test was used. Results: Retinal detachments were observed in 85.7% of group 1 and 33.3% of group 2 at the end of the follow-up (p < 0.01). No major systemic complications were observed. Conclusions: Combined therapy seems to be useful for treating experimental PVR.
Developmental Expression of GABAA Receptors in Retinal Transplants
Authors: Sharma Rajesh Kumar
Published: April 2003

γ-Aminobutyric acid (GABA) has transiently been found in certain retinal cells during development, and thus it has been suggested that besides its role as an inhibitory neurotransmitter, it also plays a role during the development of the retina. Further it has been suggested that this developmental role of GABA is mediated through GABAA receptors. Retinal cell transplants are being tried for the treatment of degenerative retinal disorders. Even though the donor tissue continues to proliferate, to develop and to differentiate after transplantation, its development is not entirely normal. Various neurotransmitters have been found in retinal transplants, but the receptors, which are needed for their action, have not been demonstrated. It was therefore of interest to see the expression of GABAA receptors during the development of the transplants. Embryonic day (E) 15 rabbit retinas were transplanted into the eyes of adult rabbits. Transplants were allowed to survive for various times so that the grafts attained the equivalent ages of (donor age + survival time) E 19, 21, 26, 29 and postnatal (PN) day 2, 5, 9, 19 and 95. On formaldehyde-fixed cryostat sections of the transplant tissue immunohistochemistry was performed. Antibodies against the α1 and β2/3 subunits of the GABAA receptors were used to demonstrate these receptors. No immunoreactivity was detected in transplants of ages E 19 and 22. The GABAA receptor β2/3 subunit first appeared in E 29 transplants, whereas the GABAA receptor α1 subunit was first detected at PN 2. At these ages faint immunoreactivity was detected in certain plexiform layers in the transplants. In older ages the immunoreactivity increased and also appeared in certain cells lying in between the rosettes along with the plexiform layers that are equivalent to the inner and the outer plexiform layers of the normal retina. The development of the GABAA receptor α1 and β2/3 subunit immunoreactivity compared well with that during the development of the normal retina. The results suggest that GABA present in the retinal transplants can exert its action through its receptors.
Protein Kinase C Isoenzyme Expression in Retinal Cells
Authors: Moriarty Patrick , Dickson Alan J. , Erichsen Jon T. , Boulton Mike
Published: April 2003

Protein kinase C (PKC) is involved in both the physiological and pathophysiological processes in the retina and plays an important role in signal transduction. The aim of this study was to determine the PKC isoenzyme profile in three retinal cell types in culture, namely RPE cells, pericytes and retinal microvascular endothelial cells. Confluent cultures were lysed and isoenzyme expression detected by Western blotting. PKC isoenzymes α, β2 and δ were observed for all three cell types while β1 was specific for RPE cells. This study has characterised the PKC isoenzyme profile in three retinal cell types and suggests that defining the cell-specific isoenzyme pattern is an important step in understanding their precise physiological role and regulation in the retina.
Colocalization of Aldehyde Dehydrogenases and Fe/NADPH-Induced Lipid Peroxidation in Tissue Sections of Rat Retina
Authors: Pinazo-Durán M. Dolores , Verdejo Cristina , Azorín Inmaculada , Renau-Piqueras Jaime , Iborra Francisco J.
Published: April 2003

Epidemiological and experimental studies suggest the involvement of lipid peroxidation (LPO) in retinal diseases. Clinicians usually prescribe antioxidants to help in the treatment of proliferative diabetic vitreoretinopathy and age-related macular degeneration. In spite of this, these processes inexorably induce visual impairment and may progress towards blindness. In addition to other pathogenic mechanisms not fully understood, it may be that peroxidic aldehydes from LPO occurring in the eyes, acting as cytotoxic chemicals, mediate in these chronic disorders. To test the mechanisms of removing peroxidic aldehydes from retinal cells and in an attempt to understand long-lasting changes induced by LPO, the distribution and activity of aldehyde dehydrogenases (ALDH) in the rat retina were studied and compared with the LPO sites induced by iron/nicotine adenine dinucleotide phosphate. Histochemical and immunocytochemical assays revealed the colocalization of LPO and ALDH, mainly in the photoreceptors and inner retinal layers. This suggests the involvement of ALDH in detoxifying peroxidic aldehydes from the retina. Any change in ALDH retinal expression and distribution might be of crucial importance in assessing the paths of LPO-mediated vitreoretinopathies. Further research is needed to evaluate these findings and their application to new ophthalmic therapy.
Blue-on-Yellow Perimetry to Evaluate S Cone Sensitivity in Diabetics
Authors: Nomura Ryoji , Terasaki Hiroko , Hirose Hiroshi , Miyake Yozo
Published: April 2003

Blue-on-yellow (B/Y) perimetry was performed on 31 patients with non-insulin-dependent diabetes mellitus to study the loss of sensitivity to short wavelengths. Of these patients, 21 were without retinopathy (NDR) and 10 had early background retinopathy (SDR). Eleven normal subjects served as controls. The results were compared to white-on-white (W/W) perimetry. Foveal sensitivity determined by B/Y and W/W perimetry showed no significant difference between NDR, SDR and normals. However, the mean sensitivity in the central 30-degree area and that in the upper half of the central 20- to 30-degree concentric circular field were significantly decreased in B/Y perimetry in SDR patients (p < 0.05, p < 0.01, respectively). No significant sensitivity loss was detected in the W/W test. We conclude that there is a blue cone system sensitivity loss in the central 30-degree area, particularly in the upper half of the visual field and the paracentral area in diabetic patients with early background retinopathy.
Intravitreal Trovafloxacin against Experimental Staphylococcus epidermidis Endophthalmitis
Authors: Karaküçük Sarper , Mirza Ertuǧrul , Sümerkan Bülent , Okten Turhan
Published: April 2003

This study was designed to test the effects of intravitreal trovafloxacin on an experimental rabbit model of Staphylococcus epidermidis endophthalmitis. Out of 26 rabbits, 22 were given intravitreal S. epidermidis (100,000 CFU). At 24 h, group 1 (8 rabbits) and, at 48 h, group 2 (8 rabbits) received 100 µg intravitreal trovafloxacin. Group 3 (6 rabbits) was used as inoculated but untreated controls. Four rabbits (group 4) were used as uninfected controls. Clinical scores were calculated at 24, 48 and 72 h. Microbiological and histopathological scorings were made. Microbiological analysis showed that trovafloxacin administered at 24 or 48 h significantly reduced the number of bacteria compared to the untreated group. We conclude that trovafloxacin applied at 24 or 48 h is effective against S. epidermidis endophthalmitis in this experimental rabbit model.
F2 Isoprostanes, Potential Specific Markers of Oxidative Damage in Human Retina
Authors: Nourooz-Zadeh Jaffar , Pereira Paulo
Published: April 2003

F2 isoprostanes (F2-IPs) are a series of prostaglandin-F2(PGF2)-like compounds produced during peroxidation of arachidonic acid (AA) by a mechanism independent of the cyclo-oxygenase. Of these, 8-epi-PGF2α has proved a reliable marker of oxidative stress in studies both in vitro and in vivo. Human retinas (n = 28) were obtained from healthy donors (age 15–59 years) and analysed for the content of free (non-esterified) as well as total (sum of free and esterified) F2-IPs. Retina tissue was homogenised, total lipids were partitioned with ethyl acetate and isoprostanes were isolated by chromatography on an NH2 cartridge. After formation of pentafluorobenzyl ester and trimethylsilyl derivatives, F2-IPs were analysed by negative ion-chemical ionisation mass spectrometry using tetradeuterated PGF2α as the internal standard. Analysis of retina samples revealed the presence of measurable amounts of esterified 8-epi-PGF2α (mean: 81.71 µg/g AA; range: 3.29–187.89 µg/g AA) but not free F2-IPs. There was no correlation between age and content of 8-epi-PGF2α. Detection of esterified F2-IPs in human retina provides the first direct evidence for free-radical-catalysed peroxidation of AA in retinal tissue. Analysis of F2-IPs should provide new opportunities for studying the implications of oxidative injury in various diseases of retina, including diabetic retinopathy and age-related macular degeneration.
Disjunctive Optokinetic Nystagmus in a Naturally Esotropic Macaque Monkey: Interaction between Nasotemporal Asymmetries of Versional Eye Movement and Convergence
Authors: Yildirim Cem , Tychsen Lawrence
Published: April 2003

Objective: To assess the interaction between versional and vergence eye movements in normal and strabismic monkeys. Methods: Horizontal optokinetic nystagmus (OKN) and vergence were measured using the magnetic scleral search coil technique in a normal adult monkey and a strabismic monkey who had naturally occurring early-onset esotropia. Mean eye velocity and vergence angles were calculated during the slow phases of OKN. Results: The strabismic monkey had a nasotemporal asymmetry of OKN favoring nasally directed motion in each eye. During monocular optokinetic stimulation, mean eye velocities were substantially greater for the adducting as compared to the abducting eye. The velocity of the abducting eye was between 55 and 80% of the velocity of the adducting eye (p < 0.01). As a consequence of the disjunctive movements, the eyes converged an average of 4 ± 2.8° during OKN. Saccadic analysis documented normal lateral rectus function in each eye. Neither an OKN asymmetry nor disjunctive OKN was observed in the normal monkey. Conclusion: Disjunctive OKN in the esotropic monkey suggests that the cerebral maldevelopment responsible for nasally biased OKN also contributes to nasal biases in vergence pathways.
Effects of Topical Clonidine on Prostaglandin-E2-Induced Aqueous Flare Elevation in Pigmented Rabbits
Authors: Watanabe Kazuhiko , Hayasaka Seiji , Hiraki Shigeyoshi , Matsumoto Masayuki , Kadoi Chiharu , Nagaki Yasunori , Hayasaka Yoriko
Published: April 2003

We evaluated the role of topical clonidine on experimental ocular inflammation. Transcorneal diffusion of prostaglandin (PG) E2, 7.09 × 10–2 mmol/l, with the use of a glass cylinder was employed to produce aqueous flare elevation in pigmented rabbits. Clonidine was topically administered and yohimbine was injected intravenously. Aqueous flare was measured with a laser flare cell meter. Topical instillation of 0.25% clonidine inhibited 89% of PGE2-induced aqueous flare elevation. Instillation of clonidine at 60 or 30 min before and 10 min after PGE2 inhibited flare significantly. Pretreatment with intravenous yohimbine decreased the clonidine-induced inhibition of the flare elevation in a dose-dependent manner. It is possible that the anti-inflammatory action of topical clonidine may be mediated partly by α2-receptors.
Distribution and Isoform Characterization of Type XII Collagen in Bovine Cornea
Authors: Kato T. , Nakayasu K. , Kanai A. , Nishiyama T. , Imamura Y. , Hayashi T.
Published: April 2003

Streptavidin peroxidase immunohistochemistry and immunoelectron microscopy were used to determine the localization of type XII collagen in sections from bovine corneas. Type XII collagen extracted from bovine cornea and skin was assayed by Western blotting. Immunohistochemical experiments showed that type XII collagen was restricted to the corneal stroma; it was not present in corneal epithelium, epithelial basement membrane, Descemet’s membrane or endothelium. Type XII collagen was distributed throughout the corneal stroma, and it was prominently localized at the superficial stroma. Immunoelectron-microscopic examination demonstrated that type XII collagen was regularly found along the surface of banded collagen fibrils with a periodic distribution. By Western blot analysis, we observed that extracts from bovine cornea contained both the long and short isoforms of type XII collagen, whereas extracts from bovine skin contained only the short isoform. The homogeneous distribution and/or presence of the long isoform of type XII collagen may be related to the characteristically regular arrangement of collagen fibrils and thereby the transparency of corneal tissue.
The Suppressive Effect of Tecogalan Sodium on in vitro Angiogenesis via the Periendothelial Proteolytic Activities
Authors: Yoshikawa Hiroshi , Ishibashi Tatsuro , Hata Yasuaki , Inomata Hajime , Sueishi Katsuo
Published: April 2003

The exact mechanisms of the angiostatic effect by tecogalan sodium (TS) remain unclear. We examined the effects of TS on in vitro angiogenic activity, proteolytic activity and proliferation of retinal vascular endothelial cells (RECs). TS markedly inhibited the in vitro angiogenic activity of RECs although the growth inhibition of RECs was small. TS apparently decreased the cell-associated urokinase-type plasminogen activator (uPA) activity and matrix metalloprotease 1 (MMP-1) activity even in the presence of anti-bFGF IgG. Thus, the suppression of the periendothelial matrix-degrading activities related to uPA and MMP-1 is suggested to be another possible mechanism of the antiangiogenic effect of TS, besides its prevention of bFGF REC binding which has previously been reported.
Cholesterol Content of Focal Opacities and Multilamellar Bodies in the Human Lens: Filipin Cytochemistry and Freeze Fracture
Authors: VanMarle Jan , Vrensen Gijs F.J.M.
Published: April 2003

Adult human lenses with focal opacities were processed for normal as well as freeze fracture electron microscopy. Cholesterol was demonstrated using filipin cytochemistry. Filipin cytochemistry in combination with freeze fracture revealed that the amount of cholesterol in the normal fibre membranes was fully comparable with the amount of cholesterol in the deviating membranes of the focal opacities and the multilamellar bodies. As regards the cholesterol/phospholipid ratio, the deviating membranes have the same state of maturation as the surrounding normal lens fibre membranes, which implies that their synthesis is as highly coordinated as the synthesis of the normal lens fibre membranes.
Universal Opacity Standard for Scheimpflug Photography
Authors: Qian Wen , Söderberg Per , Chen Enping , Philipson Bo
Published: April 2003

Purpose: To develop a universal standard for comparison of the results from different studies using Scheimpflug photography. Material and Method: A suspension including polystyrene spheres was selected as the universal standard. The polystyrene suspension was diluted into 10 concentrations by adding spectroscopic quality water. An artificial eye chamber was designed to hold the diluted suspension for photography. Each concentration was photographed by both a Topcon SL-45 slit-lamp camera and a Nidek EAS-1000 system. The intensity of back-scattered light was analyzed statistically. Results: The relationship between the concentration of the polystyrene suspension and the internal gray scale step within the Topcon SL-45 camera can be described by a second-order polynomial. The relationship between the concentration of the polystyrene suspension and the measurement of the Nidek EAS-1000 system can also be expressed by a second-order polynomial. The relationship between the Topcon SL-45 camera and the Nidek EAS-1000 system is linear. Conclusions: The results of lens nuclear opacity measured with different Scheimpflug cameras can be compared using the method established in the study. The linear relationship between the Topcon SL-45 and Nidek EAS-1000 systems can be used to convert measurements from one system to the other.
Matrix Metalloproteinase 2 Activation in Cultured Corneas
Authors: Smith Valerie A. , El-Rakhawy Amro , Easty David L.
Published: April 2003

Purpose: Corneas that are maintained in tissue culture medium shed their epithelial cells and repopulation following graft surgery is an essential facet of the healing process. Failure to do so may be a result of structural damage to the epithelial basement membrane of a donor cornea. The purpose of the present investigation was to ascertain whether MMP-2, the matrix metalloproteinase produced by corneal keratocytes, may be activated during storage and hence cleave the type IV collagen component of the epithelial cell basement membrane. Methods: Fresh and transplant rejected corneas that had been stored in culture medium for varying time periods and of known donor age were collected. The soluble protein fractions of these corneas were obtained. Their MMP-2 proteins were visualised by zymography on SDS gelatin polyacrylamide gels and assayed for activity against nitrophenyl acetate and denatured [3H]type I collagen. Results: The stromal tissue of fresh, normal corneas produced inactive MMP-2 of Mr 66,000. Although the cultured corneas did not up-regulate MMP-2 production, they contained additional MMP-2 activities of Mr 62,000 and Mr 43,000. The appearance of these additional MMP-2 activities correlated with corneal culture time but not donor age. The ability to cleave denatured [3H]type I collagen correlated with the appearance of the Mr 43,000 activity but not the Mr 62,000 activity. Conclusion: Activated MMP-2 is produced in cultured corneas. For this reason the corneas donated for all graft procedures should not be held in culture medium for periods exceeding 4 weeks.
Effect of a Nitric Oxide Synthase Inhibitor on Lens-Induced Myopia
Authors: Fujikado Takashi , Tsujikawa Kaoru , Tamura Manabu , Hosohata Jun , Kawasaki Yoshimi , Tano Yasuo
Published: April 2003

Purpose: It has still not been determined whether the retinal mechanism causing form-deprivation myopia (FDM) is different from that causing lens-induced myopia (LIM). We previously reported that FDM was blocked by an intravitreal injection of the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). In this study, we investigated the effect of L-NAME on LIM in chicks. Method: The left eyes of 6-day-old chicks were injected with 30 µl of nontoxic concentrations of L-NAME (≤360 mM) or saline. The right eyes were injected with 30 µl of saline. A –16 dpt lens was placed in front of the left eye for 6 days. Another group of 6 chicks were injected with 180 mML-NAME (left eye) and with saline (right eye) before placing –16 dpt lenses in front of both eyes. After removing the lens, the refraction and the axial length were measured. The effect of L-NAME (180 mM) on the retina of a separate group of chicks was examined by electroretinography 60 min after an intravitreal injection in non-LIM-treated eyes. Results: The eyes of chicks that were injected with 180 or 360 mML-NAME were less myopic and had significantly shorter axial lengths than control eyes. A significant decrease of the On response and an increase of the Off response were observed. Conclusion: The injection of L-NAME into developing chick eyes that were then covered with a –16 dpt lens resulted in a modifications of retinal function and an inhibition of the development of myopia. These results, combined with the earlier findings, suggest that NO modulates a common retinal pathway that leads to both LIM and FDM.
Facilitatory and Neurotoxic Effects of Intravitreal Ornithine on the Electroretinographic Responses of Albino Rats
Authors: Mizota Atsushi , Sato Eiju , Adachi-Usami Emiko
Published: April 2003

The effect of an intravitreal injection of ornithine on the retina of rats was studied electroretinographically. Rats were injected intravitreally with 5 µl of 0.02, 0.25 and 0.5 M ornithine. Electroretinograms (ERGs) were recorded before, and 1, 3 and 9 days after the injection. High doses of ornithine (0.5 M) reduced while low doses (0.02 M) enhanced the ERG amplitudes. The implicit time of the a-wave was delayed at all concentrations after ornithine injection, which suggests that implicit times may be a more sensitive parameter of the ornithine effect. There were significant changes in the stimulus intensity necessary to obtain the one half of the maximum amplitude of the b-wave that may have been caused by damage of the photoreceptors and retinal pigment epithelium cells by ornithine. We conclude that the effect of ornithine on retinal function is dose dependent and can either enhance or depress the ERG amplitudes.
Evidence for Intraocular Synthesis of Kynurenic Acid, a Putative Endogenous Neuroprotectant
Authors: Żarnowski Tomasz , Rejdak Robert , Zagórski Zbigniew , Kocki Tomasz , Kleinrok Zdzisław , Turski Waldemar A.
Published: April 2003

Kynurenic acid (KYNA), an excitatory amino acid antagonist preferentially active at glycine binding site of the NMDA receptor, has been previously identified in the brain. This study was designed to examine its presence in the rabbit vitreous humor. Mean (± SD) level of KYNA in the vitreous was 22.3 ± 3.9 pmol/ml as determined by HPLC. Intravitreal administration of 10 mmol aminooxyacetic acid (AOAA), a KYNA synthesis inhibitor, diminished its production by 9.6% after 2 h, 47.8% after 24 h and 21.5% after 48 h. It can be concluded that AOAA decreases the intravitreal concentration of KYNA, providing evidence of its intraocular origin.
Methicillin-Resistant Staphylococci and Ofloxacin-Resistant Bacteria from Clinically Healthy Conjunctivas
Authors: Watanabe Kazuhiko , Numata-Watanabe Konomi , Hayasaka Seiji
Published: April 2003

We evaluated the existence of methicillin (DMPPC)-resistant staphylococci and ofloxacin (OFLX)-resistant bacteria among preoperative patients at an eye clinic. Bacterial growth was studied in 194 conjunctival specimens of 125 preoperative patients without signs of ocular infection. Specimens were evaluated for growth of bacteria on Drigalski’s plates, blood agar plates, or chocolate agar plates for 2 days at 37°C. Susceptibilities of the strain to DMPPX, OFLX, minocycline (MINO), gentamicin (GM), erythromycin (EM), cefmenoxime (CMX), chloramphenicol (CP), and sulbenicillin (SBPC) were determined by the disk diffusion method. When DMPPC-resistant Staphylococcus aureus (MRSA) or DMPPC-resistant coagulase- negative staphylococci (MRCNS) were isolated, the susceptibility of the isolated strains to vancomycin (VCM) was additionally examined by the disk diffusion method. Of the 125 preoperative patients (194 eyes), 109 patients (159 eyes) had positive bacterial growth. Methicillin-resistant Staphylococcus aureus (MRSA) were positive in 1 patient. Methicillin-resistant coagulase-negative staphylococci (MRCNS) were positive in another patient. Two eyes with MRSA or MRCNS growth were treated with topical instillation of VCM, which was more sensitive than MINO and GM. They underwent the planned surgery after two subsequent tests showing negative growth. Of 120 isolated coagulase-negative staphylococci (CNS) 8 (6.7%) were resistant to OFLX. OFLX-resistant CNS were sensitive to MINO, CMX, and CP, but also resistant to SBPC. Of 114 isolated aerobic gram-positive rods (GPR), 55 (48.2%) were resistant to OFLX. OFLX-resistant aerobic GPR were sensitive to MINO, CMX, SBPC, and DMPPC. The 157 eyes with positive bacterial growth other than MRSA were treated with topical instillation of sensitive antibiotics. The present findings indicate that DMPPC-resistant staphylococci and OFLX-resistant bacteria exist in conjunctivas without signs of infection.
Turnover and Migration of Meibomian Gland Cells in Rats’ Eyelids
Authors: Olami Yael , Zajicek Gershom , Cogan Michael , Gnessin Hadassah , Pe’er Jacob
Published: April 2003

Purpose: The object of this study is to determine the velocity and migration course of meibomian gland cells. Materials and Methods: Twenty-seven adult rats weighing about 200 g were injected intraperitoneally with a single dose of 0.5 µCi [3H]-thymidine/g body weight. Three rats were sacrificed 1 h after injection and 3 rats each on days 3, 6, 9, 12, 15, 18, 21 and 28 after injection. The eyes and eyelids were removed in one piece, fixed in formalin, embedded in paraffin and cut into 5-µm-thick vertical sections along the pupillary-optic nerve axis. The sections were dipped in liquid autoradiographic emulsion, exposed for 3 weeks, and stained with HE. Meibomian glands were scanned in the lower eyelid of the left eye using an ocular micrometer grid. In each scan the basement membrane of each acinus served as a point of origin. Along the entire gland two parameters were noted for each nucleus with three grains or more: the distance from the basement membrane (Y) and grain count. Results: This study demonstrates for the first time the exact timing and direction of meibomian gland cell migration. We have shown that the cells migrate from the basement membrane to the center of the acinus at an average rate of 0.62 ± 0.11 µm/day. Cell generation time was an average of 4.1 days. Conclusions: The stem cells of meibomian glands lie at the circumference of each acinus. These cells migrate synchronously with a constant velocity towards the center of the acinus, and are secreted as sebaceous material.
Effects of Atropine and Propranolol on Retinal Vessel Diameters during Isometric Exercise
Authors: Jandrasits Kerstin , Polak Kaija , Luksch Alexandra , Stark Bernhard , Dorner Guido T. , Eichler Hans-Georg , Schmetterer Leopold
Published: April 2003

Purpose: There is controversy regarding the nervous control of retinal blood vessels in humans. Most in vitro studies indicate that the intraocular part of the central retinal artery lacks autonomic innervation. We investigated the response of retinal vessels to isometric exercise during blockade of β-receptors (propranolol) or muscarinic receptors (atropine). Methods: Twelve healthy subjects performed squatting for 6 min during infusion of either propranolol atropine or placebo. Blood pressure and pulse rate were measured non-invasively. Retinal vessel diameters were measured continuously using the Zeiss Retinal Vessel Analyser. Results: Squatting induced a significant increase in blood pressure and pulse rate, which was paralleled by a decrease in retinal vein and artery diameters. Atropine did not change the retinal vessel response to isometric exercise. Propranolol significantly blunted the exercise-induced vasoconstriction in retinal arteries. Conclusion: This result likely indicates propranolol-evoked vasoconstriction in the extraocular parts of the central retinal artery during isometric exercise.
Specific Labeling of Lens Aldehyde Dehydrogenase Class 1 from 3H-Cholesterol or Its Derivatives
Authors: Cenedella Richard J.
Published: April 2003

We investigated the possibility that sterols could covalently modify ocular lens cell proteins. Incubation of cultured bovine lens epithelial cells (BLEC) with 3H-cholesterol led to the labeling of a cytosolic protein of about 52 kD. Two-dimensional electrophoresis of the BLEC soluble proteins and fluorography revealed one labeled protein of 52 kD, pI = 6.6, plus a weakly labeled, slightly more acidic protein of the same size. MALDI-MS analysis of both proteins recovered from duplicate gels indicated both to be aldehyde dehydrogenase class 1 (ALDH-1). The identity was confirmed by immunoprecipitation with antiserum to ALDH-1. Alkaline hydrolysis of 3H-labeled ALDH-1 released most of the radiolabel as compounds much more polar than cholesterol. We speculate that lens ALDH-1 can participate in the oxidation of cholesterol or its derivatives to unidentified sterol carboxylic acids and that the labeled protein reflects capture of ALDH-1 with sterol intermediates covalently bound to the enzyme in ester linkage. Lens ALDH-1 might, therefore, participate in the detoxication of polar sterols.
Dryness Symptoms, Diagnostic Protocol and Therapeutic Management: A Report on 1,200 Patients
Authors: Versura Piera , Cellini Mauro , Torreggiani Alberto , Profazio Vincenzo , Bernabini Benedetta , Caramazza Roberto
Published: April 2003

Purpose: To report the diagnostic and therapeutic data obtained from 1,200 patients suffering from dry eye symptoms not due to Sjögren’s syndrome or other auto-immune diseases. Methods: Schirmer test I, ferning test, breakup time, vital dye staining, brush and imprint cytology were performed; data were grouped into diagnostic profiles, and the therapy was prescribed according to these. Results: Eight diagnostic profiles were identified. Dry eye was diagnosed in 57.1% of patients; the remaining 42.9% were found to suffer from eye discomfort or conjunctivitis of different aetiologies. Conclusions: Subjective symptoms of dryness can hide diseases other than dry eye; combined clinical and laboratory tests are requested to make a diagnosis. Our experience indicates that a therapy prescribed on the basis of diagnostic profiles provides relief in 79.1% of cases.
Gene Transfer by Adenovirus in Rabbit Iris Sphincter Muscle
Authors: Yoshitomi Takeshi , Sakamoto Taiji , Ohnishi Yoshitaka
Published: April 2003

The effect of insertion of an exogenous gene on smooth muscle function in rabbit iris sphincter muscle was investigated. An adenoviral vector encoding the bacterial LacZ gene (AdLacZ, 107 pfu) and viscoelastics were injected into the posterior chamber of eyes of albino rabbits. Three days after injection, the effects of acetylcholine (Ach), carbachol (Carb), substance P (SP) and electrical field stimuli on isolated iris sphincter were investigated using isometric tension-recording methods. X-Gal histostaining showed that iris sphincter smooth muscle cells were transfected in 7 of 11 muscle strips. Contraction-response curves for Ach, Carb or SP were not different from control. We conclude that the iris sphincter muscle can be gene-transfected by posterior chamber infusion of an adenoviral vector with viscoelastics. Adenovirus-mediated gene transfer per se had no measurable effect on tension development.
Heat Shock Protein 70 Expression Increased in Rabbit Müller Cells in the Ischemia-Reperfusion Model
Authors: Gohdo Takashi , Ueda Hideho , Ohno Shinichi , Iijima Hiroyuki , Tsukahara Shigeo
Published: April 2003

Heat shock protein 70 (HSP70) expression in the rabbit retina was evaluated in the ischemia-reperfusion model. Ischemia was induced by increasing the pressure in the anterior chamber, and the retinas were collected 1 or 12 h after reperfusion. HSP70 expression was examined by Western blot, confocal laser scanning microscopy and immunoelectron microscopy. Western blot showed that HSP70 was significantly increased in the retina 12 h after reperfusion, compared with normal control or 1 h after reperfusion. Confocal microscopy demonstrated that HSP70 was constitutive in Müller cells and that its expression was increased 12 h after reperfusion. Electron microscopy showed that glycogen-like granules were significantly decreased with prominent endoplasmic reticulum 1 h after reperfusion. Twelve hours after reperfusion, however, the density of glycogen-like granules was restored, and immunoelectron microscopy indicated that HSP70 was associated with the organelles of the Müller cells. Taken together, these data suggest that HSP70 in Müller cells plays a role in accommodation to stress.
Detection of Mutations in Argentine Retinoblastoma Patients by Segregation of Polymorphisms, Exon Analysis and Cytogenetic Test
Authors: Dalamon Viviana , Surace Ezequiel , Borelina Daniel , Ziembar Maria , Esperante Sebastian , Francipane Liliana , Davila Maria , Parma Diana , Szijan Irene
Published: April 2003

The aim of this study was to detect chromosomal and molecular abnormalities in 16 Argentine families with retinoblastoma (RB). Chromosomes were analyzed by G-banding, DNA from leukocytes and tumors was studied by segregation of polymorphisms within RB gene (RB1) and the DNA from chorionic villus by sequencing. The karyotype of an Rb236 bilateral patient with dismorphic signs revealed a deletion in 13q13–21. Polymorphism and exon analyses showed a deletion in the 3′ end of RB1 in an Rb72 patient. The mutant RB1 allele, detected by loss of heterozygosity (LOH) in the tumor, was identified in 14 out of 18 tumors. The analysis of chorionic villus revealed a mutation, a C-to-T transition in exon 18. Molecular and cytogenetic analyses in families with RB offer valuable information on how to assess the risk of tumor development.
Corneal Toxicity of Xylazine and Clonidine, in Combination with Ketamine, in the Rat
Authors: Tita B. , Leone M.G. , Casini M.L. , Corubolo C. , Bordi F. , Guidolin D. , Fumagalli E. , Romanelli L. , Mattioli F. , Fehér J. , Saso L.
Published: April 2003

Purpose: To compare the corneal toxicity of xylazine (XYL)/ketamine (KET) with that of clonidine (CLO)/KET in the rat, in the presence or not of the α2-adrenergic antagonist yohimbine (YOH). Methods: XYL (10 mg/kg) and CLO (0.15 mg/kg) were administered subcutaneously in the rat in combination with KET (50 mg/kg), in the presence or not of YOH (2 mg/kg). Results: The corneas immediately lost transparency and luster, but recovered within 120 min. By both light and electron microscopy, a marked stromal edema and alterations of all layers were observed. In addition, XYL/KET altered the permeability of the cornea as indicated by the augmented levels of 14C-indomethacin, topically administered 30 min after the anesthetic combination. Conclusions: The mechanism of the corneal toxicity of XYL and CLO in the rat is unclear but we speculate that: (a) proptosis and inhibition of normal blinking did not play a major role because topical application of hyaluronic acid did not protect against it; corneal decompensation, edema and opacification could be due to (b) osmotic or (c) mechanical endothelial stress: the first resulting from the sudden increase of the glucose concentration in the aqueous humor due to the well-known inhibition of insulin release by α2-adrenergic agonists, and the second from the acute elevation of intraocular pressure caused by these α2-adrenergic mydriatics in the rat; (d) addition, XYL and CLO could act by directly interacting with local α2- or, possibly, α1-adrenergic receptors, whose function is still not clear but probably essential for corneal homeostasis.
Expression of Matrix Metalloproteinases 2 and 9 and Tissue Inhibitors of Metalloproteinase 1 and 2 in Inflammation-Induced Corneal Neovascularization
Authors: Ma David Hui-Kang , Chen Jan-Kan , Kim Wan-Soo , Hao Yan-Xia , Wu Hui-Chuan , Tsai Ray Jui-Fang , Hwang David G. , Zhang Fen
Published: April 2003

Purpose: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) have been linked to the angiogenic process in general. In order to understand the potential roles of MMP-2, MMP-9 and TIMPs in the corneal neovascularization process, we examined the expression and activities of MMP-2, MMP-9 and TIMPs during the course of cauterization-induced corneal neovascularization in a rat model. Methods: Neovascularization of rat corneas was induced by silver nitrate cauterization. The expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was examined by immunohistochemistry and RT-PCR. The protein activities of MMPs and TIMPs were compared in pre- and postcauterization corneas by gelatin zymography and reverse zymography, respectively. Results: MMP-2, TIMP-1 and TIMP-2 immunoreactivities were expressed in normal corneas, predominantly in the corneal epithelium. After injury, immunoreactivities of both MMPs and TIMPs were increased, notably in the healing corneal epithelium, infiltrating inflammatory cells, stromal fibroblasts and ingrowing vascular endothelial cells. The increase in gross MMP-2 enzymatic activity paralleled the maximal vascular ingrowth on day 4, while the gross MMP-9 enzymatic activity rose immediately on day 1, then decreased steadily, which paralleled the magnitude of inflammatory cell infiltration. The immunoreactivity of MMPs/TIMPs decreased significantly 2 weeks after cauterization. On day 35, MMP-2, TIMP-1 and TIMP-2 staining was seen only in corneal epithelium and vascular endothelial cells. Both the RT-PCR and reverse zymography results revealed a more constant expression of TIMP-2, while the TIMP-1 expression appeared to be more inducible. Conclusion: MMPs as well as TIMPs were upregulated in cauterization-induced corneal neovascularization, suggesting that both may participate in extracellular matrix remodeling in the corneal wound healing, inflammation and neovascularization processes.
Microlaryngosurgery for Benign Posterior Glottal Lesions Using a Posterior Glottis Direct Laryngoscope
Authors: Kawaida Masahiro , Fukuda Hiroyuki , Kohno Naoyuki
Published: April 2003

When endolaryngeal microscopic laryngosurgery (microlaryngosurgery) with a direct laryngoscope is used to remove lesions of the posterior glottal area under endotracheal general anesthesia, the endotracheal tube interferes with the surgical field. To overcome this problem, we developed a special direct laryngoscope with a concave groove on the upper portion of its distal tip. The concave groove is used to move the endotracheal tube anteriorly, making it possible to obtain a good surgical field in the posterior glottal area. This laryngoscope facilitates the removal of posterior glottal lesions. The utility of this microlaryngosurgical technique for the removal of benign posterior glottal lesions is described.
High-Resolution Three-Dimensional Magnetic Resonance Imaging of the Vestibular Labyrinth in Patients with Atypical and Intractable Benign Positional Vertigo
Authors: Schratzenstaller Bruno , Wagner-Manslau Carola , Alexiou Christoph , Arnold Wolfgang
Published: April 2003

Benign paroxysmal positional vertigo (BPPV) is a most common cause of dizziness and usually a self-limited disease, although a small percentage of patients suffer from a permanent form and do not respond to any treatment. This persistent form of BPPV is thought to have a different underlying pathophysiology than the generally accepted canalolithiasis theory. We investigated 5 patients who did not respond to physical treatment, presented with an atypical concomitant nystagmus or both with high-resolution three-dimensional magnetic resonance imaging of the inner ear. This method provides an excellent imaging of the inner ear fluid spaces. In all 5 patients, we found structural changes such as fractures or filling defects in the semicircular canals which we did not find in control groups. One patient clinically presented with the symptoms of a ‘heavy cupula’. Whereas crosssections through the ampullary region and the adjoining utricle showed no abnormalities, there were significant structural changes in the semicircular canals, which are able to provide an explanation for the symptoms of a heavy cupula.
Intracranial Fibrosarcoma Arising 5 Years after Chemotherapy Alone for Glioblastoma multiforme in a Child
Authors: Kaminski Joseph M. , Yang Chi-Chuan , Yagmai Farivar , Movsas Benjamin , Lee Mark , Barrett John T.
Published: April 2003

We present a child diagnosed with glioblastoma multiforme during infancy and successfully treated with the ‘eight-in-one’ chemotherapy regimen, who developed an intracranial fibrosarcoma 5 years later. After resection of the fibrosarcoma, she received cranial radiation therapy and high dose chemotherapy with bone marrow transplant. She remains alive and recurrence-free 7 years following the diagnosis of her second intracranial malignancy.
Current Opinions for the Treatment of Syringomyelia and Chiari Malformations: Survey of the Pediatric Section of the American Association of Neurological Surgeons
Authors: Haroun Raymond I. , Guarnieri Michael , Meadow Jeffery J. , Kraut Michael , Carson Benjamin S.
Published: April 2003

Introduction: A variety of surgical interventions have been recommended for patients with syringomyelia and Chiari malformation. To obtain a better understanding of currently used management strategies and surgical interventions, this study evaluates current opinions in the treatment of these entities. Methods: Members of the Pediatric Section of the American Association of Neurological Surgeons (AANS) were surveyed in July of 1998. A questionnaire was designed to assess (1) management of asymptomatic and symptomatic cases; (2) signs and symptoms that warrant surgical intervention, and (3) surgical strategies. Seventy-seven of 234 surveys (33%) were returned. Responses were entered in a Microsoft Excel spreadsheet for data analysis. Results: Each year, respondents evaluated on average 10 patients with confirmed syringomyelia and operated on 7. There was substantial agreement to operate on patients with syringomyelia who had progressive scoliosis or progressive motor/sensory loss. For isolated syringomyelia without a Chiari malformation, the majority of respondents recommended shunting of the syrinx. Opinion was mixed concerning physical restrictions for asymptomatic patients with syringomyelia and Chiari malformations. For Chiari malformations, the majority of respondents recommended a minimum cervicomedullary decompression with dural patch grafting. No consensus was obtained on whether dural patch grafting should be done alone or in combination with intradural dissection or manipulation of the tonsils. Conclusion: Although many respondents agreed on the management and surgical treatment of symptomatic patients with syringomyelia and/or Chiari malformations, there was disagreement with regard to the optimal surgical procedure. Respondents rejected prophylactic surgery for their asymptomatic patients, choosing to follow them conservatively with serial imaging and neurological examinations.
Lumboperitoneal Shunting as a Treatment for Slit Ventricle Syndrome
Authors: Le Hoang , Yamini Bakhtiar , Frim David M.
Published: April 2003

Objective: Slit ventricle syndrome (SVS) has been described in hydrocephalus patients who continue to have shunt malfunction-like symptoms in the presence of a functioning shunt system and small ventricles on imaging studies. These symptoms usually present years after shunt placement or revision and can consist of headache, nausea and vomiting, lethargy and decreased cognitive skills. Treatments offered range from observation, medical therapy (migraine treatment) and shunt revision to subtemporal decompression or cranial vault expansion. We describe a subset of patients with SVS who were symptomatic with high intracranial pressure (ICP) as measured by sedated lumbar puncture and whose symptoms completely resolved after lumboperitoneal shunt (LPS) placement. Methods: Seven patients with a diagnosis of SVS underwent lumboperitoneal shunting. The age at shunting ranged from 3 to 18 years. Most had undergone recent ventriculoperitoneal shunt (VPS) revisions for presentation of shunt malfunction-like symptoms. Despite this, all remained symptomatic and underwent a sedated lumbar puncture to measure opening pressure (OP). All had high OP in spite of a functional VPS and underwent LPS placement. Results: All 7 patients had a prolonged period of overdrainage symptoms after lumboperitoneal shunting that resolved completely over several weeks. The initial etiology of hydrocephalus was reported to include trauma, aqueductal stenosis and intraventricular hemorrhage of prematurity. Two patients required revision of their LPS, after which their symptoms again resolved. Conclusion: In a certain subset of patients with SVS who are symptomatic from increased ICP, placement of an LPS is an effective treatment option. It appears that this subgroup of patients previously treated with ventriculoperitoneal shunting behave in a fashion similar to pseudotumor cerebri patients and respond well to lumboperitoneal shunting.