Retinal Disorders (retinal + disorders)

Distribution by Scientific Domains

Selected Abstracts

Anthocyanins Protect Against A2E Photooxidation and Membrane Permeabilization in Retinal Pigment Epithelial Cells,

Young P. Jang
ABSTRACT The pyridinium bisretinoid A2E, an autofluorescent pigment that accumulates in retinal pigment epithelial cells with age and in some retinal disorders, can mediate a detergent-like perturbation of cell membranes and light-induced damage to the cell. The photodynamic events initiated by the sensitization of A2E include the generation of singlet oxygen and the oxidation of A2E at carbon-carbon double bonds. To assess the ability of plant-derived anthocyanins to modulate adverse effects of A2E accumulation on retinal pigment epithelium (RPE) cells, these flavylium salts were isolated from extracts of bilberry. Nine anthocyanin fractions reflecting monoglycosides of delphinidin, cyanidin, petunidin and malvidin were obtained and all were shown to suppress the photooxidation of A2E at least in part by quenching singlet oxygen. The anthocyanins tested exhibited antioxidant activity of variable efficiency. The structural characteristics relevant to this variability likely included the ability to form a stable quinonoidal anhydro base at neutral pH, a conjugated diene structure in the C (pyrane) ring, the presence of hydroxyl groups on the B (benzene) ring and the relative hydrophobicity conferred by the arrangement of substituents on the B ring. Cells that had taken up anthocyanins also exhibited a resistance to the membrane permeabilization that occurs as a result of the detergent-like action of A2E. [source]

2243: Update on inherited ocular developmental disease

Purpose To provide an overview of progress in understanding of the genetics of developmental ocular disease. Methods A systematic review, including case presentations, to illustrate insights into genes underlying developmental ocular disorders: Results Studies suggest that, in developed countries, between a third and a half of the diagnoses underlying childhood blind or partial-sighted registration are genetic while a number of other ,non-genetic' conditions also have a substantial genetic contribution. Such a figure is likely to be an underestimate. Although most of these conditions are rare, many of the issues regarding diagnosis and counselling apply to the group as a whole and it is therefore possible to consider a common approach to many aspects of their clinical management. An important challenge, for example, is to improve genetic counselling for patients affected by, and at risk of, disorders that may be caused by a genetic change in one of many possible genes, which typifies many inherited conditions associated with blindness (developmental ocular disorders, early-onset retinal dystrophies, congenital cataract). Most diagnostic genetic testing currently being undertaken focuses on single genes; this will be illustrated for ocular conditions such as retinoblastoma, Norrie disease and microphthalmia. However future prospects will focus upon use of new higher throughput technologies (e.g Microarray technologies). Conclusion The recent identification of genes underlying, for example, anophthalmia/microphthalmia spectrum (e.g. VSX2, SOX2, BCOR), anterior segment dysgenesis (e.g. PITX2, FOXC1, FOXE3) and early,onset retinal disorders (e.g. ADVIRC, RPE65) has shed light on the pathways and processes underlying a range of the biological processes underlying ocular development. [source]

Mathematical analysis of the cone ERG photopic hill: Clinical applications

Purpose: With brighter stimuli, the photopic ERG b-wave increases to a maximal value and then decreases to a plateau, a feature known as the Photopic Hill (PH). Recently, a mathematical model combining a Gaussian (GF) and a Logistic Growth (LGF) functions was developed to fit the PH (Hamilton et al., Vision Research, in press). We examined if this equation could help us sort out selected retinopathies. Methods: We compared PHs (background: 30 cd.m-2; intensities: -0.8 to 2.84 log cd.sec.m-2) obtained from normals (N=40) and patients (N=20) affected with Congenital Stationary Night Blindness (CSNB), Congenital Postreceptoral Cone Pathway Anomaly (CPCPA) and Retinitis Pigmentosa (RP) with the GL ratio [GL= Gb / (Gb+Vbmax)] were Gb and Vbmax represent the amplitude of the Gaussian and logistic (Vbmax) functions respectively. Results: The normal GL ratio is 0.60 ± 0.08 (mean ± 1SD) compared to ,1.0 in CSNB (almost pure GF) and 0.32±0.08 in CPCP [reduced GF (p<.05) and normal LF (p>.05)] patients. Six of the 8 RP patients had a GL ratio above 0.5 (mean GL= 0.70 ± 0.19) and 2 below (0.28 and 0.41). Of interest, while in some retinopathies, a decline in Gb and Vbmax occurred with disease progression (longitudinal and transversal comparisons), it did not always modify the GL ratio. Conclusions: Human PH can be dissected into two distinct and concomitant phenomena each represented by its own equation. Altghough the retinal origin of the GF and LGF awaits to be confirmed, use of this mathematical approach appears to add valuable information that will further refine the diagnosis of retinal disorders affecting the photopic (cone) pathway. Supported by CIHR and Réseau Vision. [source]

Developments in molecular genetics and electrophysiology in inherited retinal disorders

Sten Andréasson
Abstract. Retinitis pigmentosa is said to be the most frequent reason for severe visual handicap among young people in Scandinavia today. Developments in the fields of electrophysiology and molecular genetics have increased our understanding of the pathophysiology of these disorders and have also improved our clinical competence, leading to a better understanding of the patient's visual handicap and his or her prognosis. This represents the first step towards fulfilling our plan for the future, which is ultimately to cure blindness caused by the different forms of hereditary retinal degeneration. This review is based on 20 years of research at the Department of Ophthalmology in Lund. [source]

An audit of genetic testing in diagnosis of inherited retinal disorders: a prerequisite for gene-specific intervention

Monika Pradhan MS MRCOphth
Abstract Background:, There has been an exponential increase in the number of genes implicated in inherited retinal disease over the last decade, but the genetic and phenotypic heterogeneity limited mutation detection. The high cost of sequencing and long turn around times meant that gene testing was not a viable option, particularly in New Zealand. Recently, advancements including development of micro-array-based mutation analysis and non-for-profit laboratories have resulted in affordable and time-efficient testing. This has enabled genetic diagnostics to become an integral component of the work-up for inherited retinal disease. Methods:, Genetic testing for inherited retinal disorders was initiated via the Ocular Genetic Clinic in Auckland 2 years ago. A retrospective audit of genetic testing over this period was carried out. The results of these tests and outcomes are discussed. Results:, Thirty-five probands have undergone genetic testing for retinal disorders. This has included X-Linked Retinoschisis, Leber Congenital Amaurosis, Retinitis Pigmentosa, Albinism, Achromatopsia, Usher syndrome, Stargardt disease and Mitochondrial disease. Of these, 54% of tests (19/35) showed a rare variant or pathogenic mutation. Three couples have proceeded to investigate the options of prenatal diagnosis and/or pre-implantation genetic diagnosis. Conclusion:, The introduction of genetic testing, largely via disease arrays, has been highly successful at clarifying disease genotype in our cohort. It is now a timely and cost-effective investigation that should be elemental to the assessment of inherited retinal disease. Genetic testing in an opportune fashion permits genetic counselling, enables families to make reproductive choices and might allow the possibility of gene therapy interventions. [source]