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S. Yoshida, T. Carter, S. Hiriyanna, M. Othman, G. Fluery, D. Lockhart, A. Hero, C. Barlow, A. Swaroop; Gene Expression Changes Associated with Retinal Aging Identified by Gene Microarrays . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2258.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To identify changes in retinal gene expression associated with aging. Methods:We have used Murine 74A GeneChip oligonucleotide microarrays (Affymetrix, Inc.) with approx. 6000 known genes and another 6000 expressed sequence tags (ESTs). cRNA targets were generated from retina, cerebellum and hypothalamus from mice at four different time points. The arrays were scanned and fluorescence intensities analyzed using Affymetrix Microarray Suit software and two novel filtering methods, Bullfrog 4.5 and Pareto filtering, were employed to extract genes altered in aging retina (GAARs). In situ hybridization was used to examine spatial expression patterns of GAARs in the retina. Results:We show that retinal aging is associated with changes in gene expression profiles. Using multiple selection criteria to filter out the stochastic nature of aging, highly reliable GAARs belonging to chaperones and immune response were identified. Pareto filtering that takes into account monotonicity as one of the criteria revealed a subtle yet consistent decline in expression of genes associated with photoreceptor structure and phototransduction. These results were confirmed by real-time RT-PCR and in situ hybridization. A comparison of gene profiles between retina and brain showed both common and unique aging pathways. Conclusions:Aging is associated with changes in gene expression in the retina and GAARs can serve as candidate susceptibility loci for aging-dependent retinal and macular diseases.
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