bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body height and ocular dimensions in the adult population in rural Central India. The Central India eye and medical study
Authors: JONAS JB , NANGIA V , MATIN A , KULKARNI M , SINHA A , GUPTA R 
Published: November 2010

Abstract Purpose To investigate associations between anthropomorphic parameters and ocular dimensions in a typical rural society untouched by the effects of urbanization. Methods The Central India Eye and Medical Study performed in rural Central India included 4711 participants aged 30 or more years. The participants underwent a detailed ophthalmic and medical examination. Results After controlling for age, gender, level of education, and body mass index (BMI), taller subjects were more likely to have larger eyes with a longer axial length, lower corneal refractive power, deeper anterior chambers, and longer vitreous cavity . Central corneal thickness (P=0.97) and lens thickness (P=0.08) were not significantly associated with body height. Subjects with a higher BMI had shorter globes, flatter corneas and thicker corneas, thicker lenses and longer vitreous cavities. Body height as compared with the BMI had a stronger influence on the ocular biometric data. After correcting for age, gender, level of education and axial length, for each increase in body height by 10 cm or for each increase in BMI by one unit, the refractive error significantly (P<0.001) increased by 0.23 diopters and by 0.40 diopters (P<0.001), respectively. Conclusion In the rural population of Central India without urbanization associated myopization, body height and size of the eye was associated with each other. Subjects with a higher body mass index had shorter eyes, flatter and thicker corneas, and thicker lenses. Since the occurrence of some ocular diseases depends of eye size and refractive error, the results may be helpful for screening examinations and for elucidating pathogenic associations.
The utility of a rabbit model of adenovirus ocular infection
Authors: ROMANOWSKI E 
Published: November 2010

AbstractAcute adenovirus ocular infections are the most common ocular viral infections worldwide and are associated with community and medical facility epidemics. While not permanently blinding, ocular adenoviral infections are associated with significant patient morbidity, including symptomatic distress with visual disturbances which can last years, and loss of time from school or work. Currently, the treatment of these acute infections is symptomatic due to the lack of an approved antiviral. This symptomatic treatment presents a controversy of whether to treat these viral infections with immunomodulating agents (e.g. topical corticosteroids, NSAIDs, cyclosporine A), which are contraindicated for use in the treatment of the other major external ocular viral infection, HSV‐1 epithelial keratitis. The adenovirus type 5 (Ad5)/New Zealand White (NZW) rabbit ocular model has provided data for potential clinical guidelines for the use of immunomodulating agents in the treatment of adenovirus ocular infections. Moreover, this model has been used extensively to evaluate promising candidate antivirals for adenovirus. Multiple candidate antivirals have been evaluated in vivo using this model, and several have proceeded to human clinical trials. The current presentation will discuss the potential clinical guidelines for the use of immunomodulating agents, present data on potential new topical antiviral agents, discuss the potential combination therapy of an antiviral and immunomodulatory agent in the treatment of adenovirus ocular infections as well as the limitations of the model.
Commercial interest
Animal models for vaccinia virus keratitis
Authors: BRANDT C 
Published: November 2010

Abstract Purpose Studies on pathogenic mechanisms involved in viral ocular infections and testing of potential therapies requires well established quantitative animal models. We present a new model of Vaccinia virus keratitis. Methods Rabbits were infected with the Dryvax strain of Vaccinia virus and disease was scored using a modified MacDonald‐Shadduck scoring system. The model will be described and examples of the use of the model for studies of pathogenesis and testing therapeutic approaches will be presented. Results The optimum dose of virus was determined (10e5 PFU). Infiltration of neutrophils followed predominantly by CD4+ cells occurred in the cornea and the optimum therapy was determined to be topical viroptic 9 times per day for 10 days. Steroid use should be avoided. Conclusion A new model of Vaccinia keratitis has been developed that is useful for pathogenesis and therapeutic studies.
Commercial interest
Cytomegalovirus infections
Authors: ATHERTON S , ZHANG M , MARSHALL B 
Published: November 2010

AbstractEven in the era of highly‐active retroviral therapy (HAART), some HIV‐infected patients continue to develop cytomegalovirus retinitis. The purpose of this SIS presentation is to discuss how results from a mouse model of CMV retinitis using murine CMV (MCMV) may help us understand the pathogenesis of CMV infection of the retina in immunosuppressed human patients. One interesting aspect of MCMV retinitis in the mouse that has also been described in human patients is the striking juxtaposition of uninfected retinal cells that are apoptotic with cytomegalovirus‐infected retinal cells that are not apoptotic. Using in vivo approaches (using MCMV infected BALB/c mice) as well as complementary in vitro studies (using virus infected cells), our laboratory has been attempting to decipher the virus and host cells processes that contribute to this interesting pattern of pathology. In addition to consideration of the most likely virus and cell modulators that mediate this process, the possible role of this juxtaposition of infected and uninfected retinal cells in preventing panretinal infection and/or in reducing spread of the virus in the retina during cytomegalovirus infection will be discussed.
Correlation of SNPs in exon 1 of loxl‐1 gene with pseudoexfoliation syndrome in patiens from Western Greece
Authors: PANOUTSOPOULOS AA , GARTAGANIS VS , GIANNAKOPOULOS MP , PANTELI VS , GARTAGANIS SP 
Published: November 2010

Abstract Purpose Pseudoexfoliation (PEX) syndrome is a clinically important systemic disorder of the extracellular matrix characterized by pathologic accumulation of an abnormal fibrillar material in various ocular tissues. LOXL1 is a cross‐linking enzyme in extracellular matrix metabolism and is required for elastic fiber formation. Single nucleotide polymorphisms (SNPs) in exon 1 of the lysyl oxidaselike 1 (LOXL1) gene have been recently identified as strong genetic risk factors for PEX syndrome. The purpose of this project is to correlate certain Single Nucleotide Polymorphisms (SNPs) in exon 1 of the gene loxl‐1 with patients from the area of Western Greece who present PEX syndrome Methods After isolating genomic DNA from the blood of PEX syndrome and cataract patients from Western Greece, exon 1 of the loxl‐1 gene was generated by Polymerase Chain Reaction (PCR) with specific primers. The DNA samples were sent for sequencing and the haplotypes that were sequenced for the areas of the loxl‐1 exon1 SNPs were statistically processed. Results In more than 50% of the PEX syndrome patients the SNPs rs3825942 and rs1048661 that are previously associated with Exfoliation Glaucoma (XFG), were shown in our population. Moreover, a significant number of cataract patients with no PEX syndrome phenotype had the above haplotype for the loxl‐1 gene. Conclusion We have performed an analysis of LOXL1 and PEX syndrome in a Western Greece patient population and have confirmed the strong association previously reported for Icelandic and Swedish samples. Preliminary results from 50 patients show that there is strong correlation for SNPs rs3825942 and rs1048661 with patients with PEX syndrome.
Gases and the ocular vasculature
Authors: SCHMETTERER L 
Published: November 2010

Abstract Purpose The regulation of ocular blood flow and oxygenation is largely controlled by metabolic factors. Among them gases like oxygen (O2), carbon dioxide (CO2), carbon monoxide (CO) and nitroc oxide (NO) play a key role. Methods In a series of clinical trials we focussed on the role of O2, CO2, CO and NO in the control of ocular blood flow. These studies were done on healthy subjects and employed a number of techniques including laser Doppler flowmetry, color Doppler imaging and pulsatile ocular blood flow techniques. Results O2 is a very potent vasoconstrictor in the retina and optic nerve head, but not in the choroid. The mechanisms underlying this effect is not entirely clear, but appears to involve endothelin A receptors. CO and CO2 are potent vasodilators in retina, choroid and optic nerve head. NO plays a major role in the control of basal vascular tone in all ocular vessels, but is also involved in many agonist‐induced vasodilator effects. Conclusion Gases play a key role in controlling ocular blood flow. An imblanace of the production of these mediators is associated with ischemia, hypoxia and endothelial dysfunction.
Hydrogen sulphide: a new CNS mediator
Authors: OSBORNE N 
Published: November 2010

AbstractThe recent discovery that hydrogen sulphide (H2S) is an endogenously produced gaseous secondary messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential role of H2S as a retinal neuroprotective agent. In the current study we use dithiolethiones (kindly provided by Dr. Piero Del Soldato, Milan, Italy) as H2S donors and show that such substances attenuate the effect of retinal ischemia as well as oxidative and light‐induced injury to a transformed line of cells (RGC‐5 cells) in culture. Ischemia was delivered to rats by elevation of the intraocular pressure above the systolic blood pressure. Partial damage to the retina after seven days was determined by a combination of procedures which included analysis of electroretinograms, immunohistochemistry and changes in the retinal content of proteins and mRNAs known to be associated with ganglion cell function and apoptosis. Most of the changes caused by ischemia were significantly attenuated by intravitreal injection of a H2S donor directly after ischemia. Both light (400‐700nm, intensity 1000 lux) and hydrogen peroxide caused death to RGC‐5 cells in culture over a period of 24‐48 hours in a time and dose‐dependent manner, respectively. Light and hydrogen peroxide‐induced RGC‐5 cell death is by different forms of apoptosis but they are both attenuated by the H2S donor, ACS1. These initial findings demonstrate that donors of H2S may be value in the treatment of various retinal dysfunctions where oxidative stress, light or ischemia is implicated as causative fact
Carbon monoxide as a mediator in the retina
Authors: BUCOLO C , DRAGO F 
Published: November 2010

Abstract Purpose Carbonic monoxide (CO) is organic gas ubiquitously synthesized in mammalian tissues by enzyme that has constitutive and inducible forms. This gas is produced as metabolic end‐product in specific cell life phases, and may acts as atypical neuronal messenger. Evidence has recently accumulated suggesting that CO may be cytoprotective because its bioactions, including inhibition of apoptosis, platelet aggregation, complement activation, and inflammatory cytokine production. CO appears to be important to counteract the cytotoxicity caused by excessive production of reactive oxygen (ROS) and nitrogen (RNS) species. Methods In vitro and in vivo models. Results Induction of heme oxygenase (HO)‐1 by hemin has been found to prevent retinal cell death after ischemia provoked by ocular hypertension in rats. The LPS‐induced expression of pro‐inflammatory cytokines, in rat eye, is also inhibited by CO. Interestingly, drugs active as inhibitors of iNOS block CO‐induced increases in cGMP in the retina.Drugs inhibiting NO formation by acting on iNOS activity have been found to potently reduce intraocular pressure. Studies from our lab showed that an increase of CO availability by hemin or carbon monoxide‐releasing molecules lower the intraocular pressure, suggesting a suppress action of iNOS‐derived NO production. Conclusion A better understanding of CO regulation may lead to new therapeutic options that are safer and more efficacious than currently available treatments for various sight‐threatening eye diseases, such as retinal degenerations.
Oxygenation of the human retina
Authors: STEFANSSON E 
Published: November 2010

Abstract Purpose Partial pressure of oxygen in the optic nerve and retina is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The PO2 is autoregulated and moderate changes in intraocular pressure, blood pressure or tissue oxygen consumption do not affect the retinal and optic nerve oxygen tension. Methods If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. Medical intervention can affect optic nerve PO2. Lowering the intraocular pressure tends to increase the optic nerve PO2, even though this effect may be masked by the autoregulation when the optic nerve PO2 and perfusion pressure is in the normal range. Results Carbonic anhydrase inhibitors increase retinal PO2 through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by indomethacin but not other cyclo‐oxygenase inhibitors. Conclusion Carbonic anhydrase inhibitors increase retinal blood flow and increase oxygen delivery. Glaucoma drugs and glaucoma surgery lower intraocular pressure, increase ocular perfusion pressure and blood flow. Demand of oxygen by retinal cells may be reduced through apoptosis and tissue atrophy, as well as active destruction of tissue by laser photocoagulation.
Heterozygous B6;C3‐Opa1Q285STOP mouse model of dominant optic atrophy displays subtle neuromuscular features with age
Authors: VOTRUBA M , TAYLOR E , DAVIES J , POWELL K , DAVIES V 
Published: November 2010

Abstract Purpose OPA1 autosomal dominant optic atrophy is a slowly progressive optic neuropathy. A neurological ‘plus’ phenotype has been reported with some OPA1 mutations, prompting further systemic evaluation of our mouse model. Heterozygous Opa1 mutant mice (B6;C3‐Opa1Q285STOP), with documented visual defects on optokinetic drum tracking and optic nerve defects on electron microscopy, were assessed. Here we explore neuromuscular aspects of the phenotype. Methods Published husbandry and genotyping protocols were used. Body weight, SHIRPA test, accelerating rotarod and visual acuity testing using the optokinetic drum was carried out. Results Mean weights of all Opa1 male and female mice over 6 months age showed a trend towards lighter weight in Opa1+/‐ mice (WT 32.74g, SD=6.0; Het 29.47g, SD=2.7 ; p> 0.05). By 20 months of age there was a statistically significant difference between WT and Hets (WT 40.6g, SD=3.1; Het 28.77g, SD=2.44; p< 0.05). SHIRPA neurological screen of 12 month old animals showed that Opa1+/‐ (Hets) were less active than wild type (WT) in an open arena (p<0.05), and less able to perform the wire hang test (p<0.05). 12 month Opa1+/‐ showed reduced mean performance on rotarod (WT 92s, SD=10; Het 70s, SD=20.9; p=0.05). Rotarod testing at 20 months was discontinued since grossly obese wild type mice were unable to perform the test and act as controls. Conclusion Opa1+/‐ mice are lighter than WT age and sex matched controls. Rotarod testing confirms a subtle neuromuscular defect in Opa1+/‐ mice in line with neurological (SHIRPA) testing.
Age‐related modifications in RPE cells
Authors: MANNERMAA E 
Published: November 2010

AbstractAge‐related macular degeneration (AMD) is a multi‐factorial polygenetic aging disease. It has been shown that RPE dysfunction predisposes neural retinal dysfunction and the development of choroidal neovascularization. The pathogenesis of age‐related macular degeneration (AMD) essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells and extracellular drusen formation, as well as the presence of chronic inflammation. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. This presence of lipofuscin decreases lysosomal enzyme activity and impairs autophagic clearance of damaged proteins which should be removed from cells. Proteasomes are another crucial proteolytic machine which degrades especially cellular proteins damaged by oxidative stress. The cross‐talk between lysosomes, autophagy and proteasomes in RPE cell protein aggregation, their role as a possible therapeutic target and their involvement in the pathogenesis of AMD is discussed. In addition, age related changes in Bruch’s membrane and choroidal blood flow may take part in the pathogenesis of AMD. This will be also discussed.
Why are retinal pigment epithelial cells so resistant to oxidative stress?
Authors: BRUNK U , KURZ T , KARLSSON M 
Published: November 2010

Abstract Purpose The functional integrity of postmitotic retinal pigment epithelial (RPE) cells is crucial for photoreceptor survival, and RPE malfunction is considered an important factor behind age‐related macular degeneration (AMD). Although RPE cells daily phagocytose large amounts of fatty acid‐rich distal photoreceptor material, their lysosomal accumulation of lipofuscin (LF) is nevertheless slow. Only late in life do humans have LF‐loaded RPE cells, which then not only have a reduced capacity to endocytose photoreceptor material but also are less capable of keeping up with normal autophagy. The latter activity is important for normal turnover of the cell’s own components. Methods ARPE‐19 cells in culture were evaluated with respect to lysosomal stability at oxidative stress. Redox‐active iron, autophagic activity (evaluation of LC3‐I and LC3‐II protein), and anti‐oxidative proteins were assayed using cytochemistry (Sulphide‐Silver Method), electron spin resonance (ESR) and western blotting for a variety of stress proteins. Results The lysosomal compartment of the ARPE‐19 cells was found remarkably resistant to oxidative stress. The SSM and ESR methods suggested low lysosomal amounts of redox‐active iron and no enhanced autophagy following oxidative stress. The normal autophagy rate was higher than in other professional scavengers. Conclusion The found low amount of lysosomal redox‐active iron explains the slow formation of lipofuscin over time and the remarkable stability that ARPE‐19 cells and their lysosomes show even under severe oxidative stress. The molecular mechanisms behind this phenomenon may be an unusual capacity to quickly export low mass iron from lysosomes to the cytosol and/or a high normal degree of autophagy of iron‐binding stress proteins.
Childhood onset retinal dystrophy in Northeastern Tunisia: phenotypic characteristics and RPE65 gene analyses
Authors: CHEBIL A , LARGUECHE L , TRIKI M , BAKLOUTI K , CHOUCHENE I , OUECHTATI F , ABDELHAK S , MUNIER F , EL MATRI L 
Published: November 2010

Abstract Purpose To describe the phenotypic characteristics of seven families with childhood onset retinal dystrophy in Northeastern Tunisia and to determine the linkage with RPE65 gene mutation. Methods Seventy subjects were concerned (18 affected patients and 52 unaffected). Ophthalmic examinations included visual function testing, fundus examination, full field ERG, spectral OCT and fluoroangiography. After patients consent, screening of RPE65 gene was performed by bi‐directional sequencing. Results All affected members had a severe retinal dystrophy with history of low visual acuity since infancy. The age at first ophthalmic examination ranged from 5 to 55 years old. Visual acuity ranged from no light perception to 2/10. Two retinal patterns were identified: the first one presented midperipheral white dot deposits, whereas the second showed midperipheral pigmented clumps without any white deposits. Atrophic and /or pigmentary macular changes were present in most patients. Mutational screening of the RPE65 gene identified an homozygous R91W mutation co‐segregating with the disease in 11 affected individuals. Two siblings were compound heterozygous for this mutation. Conclusion We identified and characterized an endemic form of early onset rod‐cone dystrophy in a consanguineous population from northeastern Tunisia, due to the prevalence of a single single homozygous missense R91W mutation in exon 4 of the RPE65 gene. This could have practical value for genetic screening strategy in young affected tunisian patients.
Principles of genetic counselling
Authors: HALL G 
Published: November 2010

Abstract Purpose To present the genetic counselling needs of families with inherited eye disease. Methods A presentation on the counselling challenges and ethical dilemmas in genetic services for inherited eye disease using case illustrations and review of research and current literature. Results Genetic counselling for families with inherited eye disease is rapidly advancing with improvements in molecular testing leading to accurate diagnosis and information for families. With increasing patient demand and expectation, families request genetic counselling to understand the inheritance pattern and the risks to themselves and their children. However, the heterogeneity, variable penetrance and overlapping phenotypes make this particularly challenging in genetic eye disease. Genetic counselling is a communication process to provide information about the genetic condition, its inheritance and to facilitate decision‐making around genetic testing and reproduction. Genetic counsellors have experience in helping individuals decide and come to terms with results from genetic testing such as pre‐symptomatic testing, childhood testing and pre‐natal diagnosis. In addition, families are often coping with the psychological burden of progressive blindness and the impact of vision loss and risk to other family members. Recent publications highlight the disparity in specialist service provision for families with inherited eye disease and calls for research and improvements in evidenced‐based practice. Conclusion Families with inherited eye disease have complex genetic counselling needs requiring multidisciplinary co‐ordination of services for accurate diagnosis, information provision, genetic testing and decision‐making, and support and follow‐up.