Gene expression profiles of mouse retina during aging

Abstract

Abstract: : Purpose: Advancing age is a strong risk factor for many eye diseases, including age–related macular degeneration (AMD). The adaptive response of the retina to aging may involve specific gene expression changes that contribute to visual dysfunction in the elderly. The goal of this study is to identify genes and pathways that are altered during aging of the retina by screening genetically homogeneous mouse retina from several different age groups using microarray technology. Methods: We isolated retina from genetically isogenic C57 BL/6 mice at four different ages (2, 6, 16, 21 months). Four replicate Affymetrix GeneChip^® Murine Genome 74Av2 arrays were hybridized with retinal RNA from each age group for a total of 16 arrays. The retina from 2 month old mice represented gene expression profiles of the adult, while data from 6, 16, and 21 months old mice allowed for the temporal identification of aging–associated changes in gene expression. Data were analyzed using Affymetrix Microarrays Suite, Data Mining Tool, Robust Multi–array Analysis, Pareto analysis and False Discovery Rate. Results: Approximately 38% of the genes on Affymetrix GeneChip^® Murine Genome 74Av2 arrays hybridized with RNA from retina. We compared gene expression in 21 months old mice with 2 months old mice and identified over 50 genes that appear to be up– or down–regulated during aging. The genes altered during aging included genes involved in cell death, signal transduction, response to stress, immune response and lipid metabolism. Comparison of the expression profiles among all age groups will distinguish genes that are involved early on in the aging process which may trigger certain pathways from those that are involved at the later stages and may represent the end point of a pathway. Conclusions: Our results suggest that aging of the retina is associated with changes in the expression of a specific set of genes regulating immune response, stress response and cell death. Identification of genes altered during aging of the retina in these genetically isogenic mice will provide new insights into the molecular pathways involved not only in normal retinal aging in humans but also in age–related retinal diseases.

Keywords: aging • retina • age–related macular degeneration