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 (Aβ). Measurement of Aβ 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 Aβ may have a role in the pathogenesis of retinopathy in OXYS rats.
KeywordsAging OXYS rats Age-related macular degeneration QTL Beta-amyloid protein
- Aβ (1-42)
Amyloid beta protein fragment (1-42)
Amyloid beta precursor protein
Age-related macular degeneration
Retinal pigment epithelium
Quantitative trait loci
Microscopy was performed in the Microscopy Centre of Institute Cytology and Genetics SB RAS. We thank A. Shvalov and S.I. Baiborodin for technical assistance and Dr. E. Rogaev for helpful discussion. This study was supported by Russian Foundation for Basic Research Grants (project 11-04-00666-a, 12-04-00091-a and 12-04-31975) and partially by Project No. 14.B25.31.0033, Resolution No. 220 of the Government of the Russian Federation of April 9, 2010.
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