Association of AMD-like retinopathy development with an Alzheimer's disease metabolic pathway in OXYS rats.

The main cause of vision loss in older individuals is age-related 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 senescence-accelerated 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 disease-free Wistar rats. Among the genes with altered expression were Picalm and Apba2, known to be participants in the processing of the beta-amyloid (Ab). Measurement of Ab 1-42 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 disease-free Wistar rats. Based on functional annotation of QTL, microarray, and ELISA results we suggest that accumulation of Ab may have a role in the pathogenesis of retinopathy in OXYS rats.