Molecular and Functional Changes Associated With Normal Aging in the Retina

Abstract

Purpose: : Advanced age is a major risk factor for age-related macular degeneration, yet little is known about the normal aging of the retina. Rods are particularly vulnerable to the effects of aging. This study aims to elucidate changes in gene expression and metabolic function associated with normal aging of retinal neurons, particularly rod photoreceptors.

Methods: : We used flow cytometry to enrich for GFP (Green Fluorescent Protein)-tagged rod photoreceptors from mouse retina at ages ranging from 1.5 to 12 months. RNA was extracted from purified rod photoreceptors and gene expression profiles were generated using Affymetrix chips. To complement these studies, mitochondrial respiratory function was compared using dissociated retinal cells from mice of different ages (ranging from 1 to 16 months old) and measuring oxygen consumption rates and extracellular acidification rates. Electroretinograms (ERGs) were also performed to measure functional change in vision with age. Quantitative polymerase chain reaction and immunohistochemistry were used to confirm expression level changes in selected genes.

Results: : Changes associated with age were found in the expression levels of several genes associated with proteolysis, angiogenesis, apoptosis, and mitochondrial function. Mitochondrial respiratory function showed little change across the spectrum of ages tested. ERGs showed decreases in scotopic a and b waves, and in photopic b waves with increasing age.

Conclusions: : Aging is a complex process that varies between cell types within the same individual. Evaluating gene profile changes associated with aging in a single postmitotic cell type should allow better insights into the photoreceptor aging process. The candidate genes found here provide a foundation for future experiments to explore potential pathways of aging and related functional adaptation.

Keywords: aging • photoreceptors • gene/expression