Journal Title
Title of Journal: Biogerontology
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Abbravation: Biogerontology
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Publisher
Springer Netherlands
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Authors: Oyuna S Kozhevnikova Elena E Korbolina Natalia A Stefanova Natalia A Muraleva Yuriy L Orlov Nataliya G Kolosova
Publish Date: 2013/08/20
Volume: 14, Issue: 6, Pages: 753-762
Abstract
The main cause of vision loss in older individuals is agerelated macular degeneration AMD—a complex multifactorial disease whose etiology and pathogenesis are not completely understood This is due to the impossibility of investigating the early stages of AMD and paucity of biological models The senescenceaccelerated OXYS rats develop retinopathy with clinical and morphological manifestations similar to AMD But the genetic determinants of its development are not known Previously we identified quantitative trait loci QTLs associated with the development of cataract retinopathy and behavioral signs in OXYS rat In this study we used bioinformatic analysis to show the enrichment of QTL region with genes associated with neurodegeneration including a pathway of Alzheimer’s disease For selected list of candidate genes we designed oligonucleotide DNA chips Using them we found small but significant changes in expression of several genes in OXYS retina compared to diseasefree Wistar rats Among the genes with altered expression were Picalm and Apba2 known to be participants in the processing of the betaamyloid Aβ Measurement of Aβ 142 in the retina showed that its level increases with age in rats and at advanced stages of retinopathy in OXYS rats its expression becomes significantly higher than that of diseasefree Wistar rats Based on functional annotation of QTL microarray and ELISA results we suggest that accumulation of Aβ may have a role in the pathogenesis of retinopathy in OXYS ratsMicroscopy was performed in the Microscopy Centre of Institute Cytology and Genetics SB RAS We thank A Shvalov and SI Baiborodin for technical assistance and Dr E Rogaev for helpful discussion This study was supported by Russian Foundation for Basic Research Grants project 110400666a 120400091a and 120431975 and partially by Project No 14B25310033 Resolution No 220 of the Government of the Russian Federation of April 9 2010
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