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Retinal Atrophy (retinal + atrophy)
Selected AbstractsCanine inhertited retinal degenerations: update on molecular genetic research and its clinical applicationJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2002C-T. Lin Inherited retinal degenerations in the dog include generalized progressive retinal atrophy, retinal pigment epithelial dystrophy, congenital stationary night blindness and day blindness (hemeralopia). The clinical phenotype and pathology of these diseases closely resemble some types of human inherited retinal degeneration, in particular retinitis pigmentosa, one of the most common inherited causes of blindness in man. Molecular genetic investigations aim to identify the genetic mutations underlying the canine inherited retinal degenerations. Two major research strategies, candidate gene analysis and linkage analysis, have been used. To date, candidate gene analysis has definitively identified the genetic mutations underlying nine inherited retinal degenerations, each in a different breed of dog, and linkage studies have identified genetic markers for a further retinal degeneration which is found in at least six different breeds. This review outlines the research strategy behind candidate gene and linkage studies and summarises recent results in the search for genetic causes of canine inherited retinal degenerations. The aim is to increase awareness of this rapidly changing field and to show how the research can be used to develop genetic tests for these diseases and thereby reduce the incidence of inherited eye disease in dogs. [source] Evaluation of RDS/Peripherin and ROM1 as candidate genes in generalised progressive retinal atrophy and exclusion of digenic inheritanceANIMAL GENETICS, Issue 3 2000M Runte Summary Generalised progressive retinal atrophy (gPRA) is a heterogeneous group of hereditary diseases causing degeneration of the retina in dogs and cats. As a combination of mutations in theRDS/Peripherin and the ROM1 genes leads to the phenotype of retinitis pigmentosa in man we first performed mutation analysis to screen these genes for disease causing mutations followed by the investigation of a digenic inheritance in dogs. We cloned the RDS/Peripherin gene and investigated the RDS/Peripherin and ROM1 genes for disease causing mutations in 13 gPRA-affected dog breeds including healthy animals, obligate gPRA carriers and gPRA-affected dogs. We screened for mutations using single strand conformation polymorphism (SSCP) analysis. Sequence analysis revealed several sequence variations. In the coding region of the RDS/Peripherin gene three nucleotide exchanges were identified (A277C; C316T; G1255A), one of which leads to an amino acid substitution (Ala339Thr). Various silent sequence variations were found in the coding region of the ROM1 gene (A536G, G1006A, T1018C, T1111C, C1150T, C1195T), as well as an amino acid substitution (G252T; Ala54Ser). By excluding the respective gene as a cause for gPRA several sequence variations in the intronic regions were investigated. None of these sequence variations cosegregated with autosomal recessively (ar) transmitted gPRA in 11 breeds. The candidate geneRDS/Peripherin obviously does not harbour the critical mutation causing the autosomal recessive form of gPRA because diseased individuals show heterozygous genotypes for sequence variations in the Miniature Poodle, Dachshund, Australian Cattle Dog, Cocker Spaniel, Chesapeake Bay Retriever, Entlebucher Sennenhund, Sloughi, Yorkshire Terrier, Tibet Mastiff, Tibet Terrier and Labrador Retriever breeds. In the following breeds the ROM1 gene was also excluded indirectly for gPRA: Miniature Poodle, Dachshund, Australian Cattle Dog, Sloughi, Collie, Tibet Terrier, Labrador Retriever and Saarloos/Wolfhound. Digenic inheritance for gPRA is practically excluded for both these genes in four breeds: Miniature Poodle, Dachshund, Labrador Retriever and Saarloos/Wolfhound. [source] Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin®) in neovascular age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 6 2010Philippe Bonnin Acta Ophthalmol. 2010: 88: 641,645 Abstract. Purpose:, Angiogenic inhibitors, alone or combined with other therapies, are believed to represent a promising treatment for neovascularization in age-related macular degeneration (wet AMD). They can maintain or improve visual acuity (VA), at least for the first 2 years. However, evolution to retinal atrophy cannot be ruled out and it may be useful to assess the effects of antiangiogenic therapy on retinal and choroidal circulation. Methods:, We carried out a pilot study in 15 patients with wet AMD. Time-averaged mean blood flow velocities (BFVs) in the central retinal, temporal posterior ciliary and ophthalmic arteries (CRA, TPCA and OA) were measured by ultrasound imaging before and 4 weeks after a single intravitreal injection of 1.25 mg bevacizumab in 0.05 ml. Patients underwent two ophthalmic examinations, before and 4 weeks after injection, including VA measurement and optical coherence tomography (OCT3) examination. Results:, In treated eyes, bevacizumab injection was followed by a significant improvement in VA (from 20/125 to 20/80; p = 0.0214), and a decrease in mean central macular thickness (from 392 ± 96 ,m to 271 ± 50 ,m; p = 0.0038). Mean BFV decreased by 10% in the CRA (p = 0.0226), 20% in the TPCA (p = 0.0026) and 20% in the OA (p = 0.0003). No effect was observed in fellow eyes. Conclusions:, Intravitreal bevacizumab acutely improved VA and reduced central macular thickness in wet AMD. Ultrasound imaging revealed that BFVs decreased in all retrobulbar arteries, suggesting that after local diffusion, bevacizumab exerts a short-term regional effect. Bevacizumab might therefore induce hypoperfusion of the whole eye, which may correspond to a vascular side-effect. [source] In vivo imaging of retinal inflammation in experimental autoimmune uveoretinitisACTA OPHTHALMOLOGICA, Issue 2009Purpose Experimental animal models are essential for us to understand the pathogenesis of human diseases. Posterior uveoretinitis can be modelled in mice with IRBP immunization (i.e. experimental autoimmune uveitis, EAU), whereas a number of mouse models are also available for age-related macular degeneration (AMD). With the advancement in new technologies, it is now possible to image inflammatory retinal changes in experimental mice in vivo none invasively. The aim of the study is to clinical revisit the traditional retinal inflammation animal models with modern imaging techniques. Methods EAU was induced in C57B/6 mice with IRBP peptide 1-20. Aged CCL2 knockout mice were used as an AMD model. Retinal inflammatory changes were imaged in vivo non-invasively using topical endoscopic fundus imaging system and the scanning laser ophthalmoscopy (SLO) system. Results Inflammatory retinal changes in the early stages of EAU were characterised as retinal oedema, vascular sheathing, multiple small retinal infiltrates or large linear retinal infiltrates. "Snow-ball"-like vitreous infiltrates were observed in the inferior part of the fundus at the peak stage of EAU. Using SLO autofluorescent (AF)-macrophages were detected at the peak stages of EAU and were located predominately around inflamed retinal venules. At the late stages of EAU, retinal scars and intraretinal neovascular membranes were observed. In the retina aged CCL2 KO mice, regional retinal atrophy and dursen-like multiple lesions were observed. Dursen-like changes were autofluorescent in SLO examination. Ex vivo confocal microscopy indicated that they were not dursen but subretinal lipofuscin-loaded microglial cells. Conclusion EAU mimics many aspects of human posterior uveoretinitis including retinal vasculitis, multifocal choroiditis. Late stage EAU could be a good model for inflammation induced retinal neovascularisation. CCL2 KO mouse is a model of dry-AMD. [source] New perspectives in retinal imaging: fundus autofluorescence and age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 2007F HOLZ Fundus Autofluorescence (FAF) imaging using confocal scanning laser ophthalmoscopy is a non-invasive method to to accurately record the topographic distribution of RPE lipofuscin in the human eye in vivo. Excessive lipofuscin accumkulation in the RPE is a common downstream pathogenetic pathway in various complex and monogenetic retinal diseases. Toxic compounds and molecular mechanisms of interference with normal cellular functions have been identified including the dominant fluorophore A2-E. Alterations in fundus autofluorescence (FAF) appearance in eyes with early and late age-related macular degeneration (AMD) can be striking. FAF patterns and distribution do not necessarily correlate with the features of interest in color or angiographic images of eyes with early or late AMD. In the prospective, multicenter FAM study distinct patterns of abnormal FAF were identified and classified in the junctional zone of geographic atrophy (GA). Areas of increased FAF outside GA were associated with variable degrees of loss of retinal sensitivity when tested with microperimetry which suggests a functional correlate of lipofuscin accumulation. Increased FAF preceded the development and enlargement of outer retinal atrophy associated with spread of absolute scotoma in eyes with AMD. Longitudinal examinations showed that the abnormal phenotypic FAF patterns serve as novel prognostic determinants which allows to distinguish fast vs. slow progressors. These findings are relevant and now used to design and carry out interventional trials with agents aimed at slowing down spread of atrophy, e.g. using visual cycle modulators to influence lipofuscinogenesis. Hereby FAF imaging also serves as a mean to accurately delineate and measure areas of GA over time in an automated fashion. A phenotype-genotype correlation was identified for a distinct FAF phenotype subset which was found to represent late-onset Stargardt macular dystrophy mimicking late-stage atrophic AMD. New imaging technologies were recently applied including simultaneous recordings of FAF images and high-resolution, spectral-domain optical coherence tomography (OCT) which allows to identify morphological correlates of abnormal FAF signals in optical biopsies. [source] | ||||||||||