Rat retinal transcriptome. Effects of aging and AMD-like retinopathy

Cell Cycle 12:11, 1745–1761; June 1, 2013; © 2013 Landes Bioscience

Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. To identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. The majority of them are related to the immune system and extracellular matrix turnover. Only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. Over 600 genes showed significant differences in expression between the two strains. These genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca2+ homeostasis and oxidative stress. The altered expression for selected genes was confirmed by qRT-PCR analysis. To our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy.

Keywords: aging, age-related macular degeneration, retinal transcriptome, RNA-Seq, OXYS rats

Abbreviations: AMD, age-related macular degeneration; RPE, retinal pigment epithelium; DE, differential expression; DEGs, differentially expressed genes; NGS, next generation sequencing; ECM, extracellular matrix; IFs, intracellular filaments; PCA, principal component analysis; FPKM, fragments per kilobase of exon model per million mapped fragments; GO, gene ontology; CNS, central nervous system.