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Retinal Pathology (retinal + pathology)
Selected AbstractsThe Y402H variant of complement factor H is associated with age-related macular degeneration but not with diabetic retinal disease in the Go-DARTS studyDIABETIC MEDICINE, Issue 5 2009A. S. F. Doney Abstract Aims, The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening. Methods, Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models. Results, The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 × 10,11). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 × 10,7). The life-time hazard ratio was 3.4 (P = 2.1 × 10,16). We found no association of Y402H with development of referable diabetic retinal disease. Conclusion, The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions. [source] Pigment epithelium-derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epitheliumGLIA, Issue 1 2001Monica M. Jablonski Abstract In conditions in which the retinal pigment epithelium (RPE) is dystrophic, carries a genetic mutation, or is removed physically, Müller cells undergo degenerative changes that contribute to the retinal pathology. We previously demonstrated that pigment epithelium-derived factor (PEDF), a glycoprotein secreted by the RPE cells with neuroprotective and differentiation properties, protects against photoreceptor degeneration induced by RPE removal. The purpose of the present study was to analyze the putative gliosupportive activity of PEDF on Müller cells of RPE-deprived retinas and assess whether protection of Müller cells was correlated with improved photoreceptor outer segment assembly. Eyes were dissected from Xenopus laevis tadpoles, and the RPE was removed before culturing in medium containing purified PEDF, PEDF plus anti-PEDF, or medium alone. Control eyes matured with an adherent RPE or in medium containing PEDF plus nonimmune serum. Müller cell ultrastructure was examined. Glial fibrillary acidic protein (GFAP) and glutamine synthetase were localized immunocytochemically, and the corresponding protein levels were quantified. In control retinas, Müller cells were structurally intact and formed adherens junctions with neighboring photoreceptors. In addition, they did not express GFAP, whereas glutamine synthetase expression was high. RPE removal dramatically altered the ultrastructure and biosynthetic activity of Müller cells; Müller cells failed to form adherens junctions with photoreceptors and glutamine synthetase expression was suppressed. PEDF prevented the degenerative glial response; Müller cells were ultrastructurally normal and formed junctional complexes with photoreceptors. PEDF also preserved the expression of glutamine synthetase at near-normal levels. The morphogenetic effects of PEDF were blocked by the anti-PEDF antibody. Our study documents the glioprotective effects of PEDF and suggests that maintenance of the proper Müller cell ultrastructure and expression of glutamine synthetase may be necessary to support the proper assembly of photoreceptor outer segments. GLIA 35:14,25, 2001. © 2001 Wiley-Liss, Inc. [source] Post-transcriptional suppression of pathogenic prion protein expression in Drosophila neuronsJOURNAL OF NEUROCHEMISTRY, Issue 6 2003Nathan R. Deleault Abstract A wealth of evidence supports the view that conformational change of the prion protein, PrPC, into a pathogenic isoform, PrPSc, is the hallmark of sporadic, infectious, and inherited forms of prion disease. Although the central role played by PrPSc in the pathogenesis of prion disease is appreciated, the cellular mechanisms that recognize PrPSc and modulate its production, clearance, and neural toxicity have not been elucidated. To address these questions, we used a tissue-specific expression system to express wild-type and disease-associated PrP molecules heterologously in Drosophila melanogaster. Our results indicate that Drosophila brain possesses a specific and saturable mechanism that suppresses the accumulation of PG14, a disease-associated insertional PrP mutant. We also found that wild-type PrP molecules are maintained in a detergent-soluble conformation throughout life in Drosophila brain neurons, whereas they become detergent-insoluble in retinal cells as flies age. PG14 protein expression in Drosophila eye did not cause retinal pathology. Our work reveals the presence of mechanisms in neurons that specifically counterbalance the production of misfolded PrP conformations, and provides an opportunity to study these processes in a model organism amenable to genetic analysis. [source] New perspectives of optical coherrence tomography in diagnosis and follow-up of macular holesACTA OPHTHALMOLOGICA, Issue 2009SA KABANAROU Purpose To compare Time Domain (TD) with Spectral Domain (SD) OCT for imaging macular holes, identify retinal pathology and correlate anatomical morphology after surgical intervention for hole closure with visual outcome. Methods 34 eyes of 34 patients with idiopathic macular holes stage II- IV were included in this study. Comparative studies were performed with both SD OCT (Heidelberg, Germany) and TD OCT (Stratus) using standard scanning protocols of 6 radial 6-mm scans through the fovea. All patients underwent a standard three port- pars plana vitrectomy. Postoperatively, all patients were evaluated using both OCTs. ETDRS visual acuities were recorded pre- and post-operatively. Results In general TD and SD OCTs showed comparable images of macular holes. However, the boundary line between the inner and outer segments of the photoreceptors was better imaged with the SD OCT preoperatively and postoperatively. Poor visual acuity postoperatively was measured mainly in cases with morphological disruption in this boundary line despite hole closure. Conclusion SD OCT imaging enhances the visualization of retinal anatomy in macular holes relative to TD OCT. [source] New insights into the pathogenic role of advanced glycation in diabetic retinopathyACTA OPHTHALMOLOGICA, Issue 2008AW STITT Purpose Retinopathy is the most common microvascular complication of diabetes. The clinicopathology of microvascular lesions and neuroglial dysfunction in the diabetic retina have been extensively studied, although the relative contribution of various biochemical sequelae of hyperglycaemia remains ill-defined. The formation and accumulation of advanced glycation endproducts (AGEs) is an important pathogenic pathway in the progression of diabetic retinopathy although some of the cellular and molecular pathologies initiated by these adducts in retinal cells remain unknown. Methods This presentation will cover several aspects of AGE-linked retinal pathology and demonstrate opportunities for therapeutic intervention. The studies outlined will cover a wide range of molecular cell biology approaches using appropriate in vitro and in vivo model systems. Results It will be demonstrated that AGEs form in vivo in the diabetic retina through the reaction of alpha-oxaloaldehydes leading to significant modifications of retinal proteins. Evidence will be presented to demonstrate that these AGEs act as significant effectors of retinal vascular and neuroglial cell dysfunction, leading to pro-inflammatory responses, growth factor imbalance and, ultimately, neurovascular lesions such as blood retinal barrier dysfunction and microvascular degeneration. The protective role of novel AGE-inhibitors will also be shown. Conclusion Evidence now points towards a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy and this review lecture will outline the current state of knowledge of AGE-related pathology in the retina at a cellular and molecular level. [source] Caspase-1/interleukin-1beta signaling in diabetic retinopathyACTA OPHTHALMOLOGICA, Issue 2008S MOHR Purpose The pro-inflammatory cytokine, interleukin-1, (IL-1,), is known to induce vascular dysfunction and cell death. Previously, we have shown that caspase-1 activity is increased in retinas of diabetic and galactosemic mice, and diabetic patients. Therefore, we investigated the role of IL-1, and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries. Methods First, we determined the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1, production and retinal capillary degeneration in diabetic and galactose-fed mice. Diabetic and galactose-fed mice were injected intraperitoneally with minocycline or tetracycline (5mg/kg). Second, we examined the effect of genetic deletion of the IL-1, receptor on diabetes-induced caspase activities and retinal capillary degeneration using IL-1 receptor knock-out mice. Results At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1, production in the retina. Long-term administration of minocycline prevented retinal capillary degeneration in diabetic (6 months) and galactose-fed (13 months) mice. Tetracycline inhibited hyperglycemia-induced caspase-1 activity in vitro, but not in vivo. Mice deficient in the IL-1, receptor were protected from diabetes-induced caspase activation and retinal pathology at 7 months of diabetes. Conclusion These results indicate that the caspase-1/IL-1, signaling pathway plays an important role in diabetes-induced retinal pathology and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy. [source] Victorian orthoptists' performance in the photo evaluation of diabetic retinopathyCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 8 2007Zoran Georgievski BAppSc(Orth)Hons Abstract Purpose:, The aim of this study was to investigate the effectiveness of orthoptists in detecting various grades of diabetic retinopathy (DR) and retinal pathology not directly associated with diabetes and to identify factors associated with best performance. Methods:, Forty-five orthoptists completed a survey comprising questions regarding their workplace experiences, plus a photo evaluation task with 36 digital fundus images. Results:, We found that orthoptists' overall performance in detecting the presence of abnormality in a series of DR images was high, the mean sensitivity being 86% and specificity 91%. The sensitivity was lower for images with minimal non-proliferative DR, but higher for those with mild,moderate and severe grades of DR. No factors were predictive of performance on the screening task. Conclusions:, Orthoptists performed extremely well, meeting the guidelines for DR screening recommended by National Health and Medical Research Council. The results indicate that orthoptists could potentially be used in DR screening models in Australia. [source] | |||||||||||||