Purchase this article with an account.
J. W. Stoddard, P. Francis, L. Johnson, M. Garred, B. Park, J. O'Malley, K. Sonmez, M. Neuringer; Retinal Gene Expression in Rhesus Monkeys with Age-Related Macular Disease. Invest. Ophthalmol. Vis. Sci. 2009;50(13):792.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The presence of a macula in the nonhuman primate retina makes these animals uniquely valuable models for studying age-related macular disease. Older rhesus monkeys commonly develop phenotypic characteristics including drusen that closely resemble early-intermediate human age-related macular degeneration (AMD). We recently demonstrated that SNPs in ARMS2 and HTRA1, two genes strongly associated with AMD in humans, are also associated with the disease in rhesus monkeys, stimulating further investigation of the genetic etiology of this disorder. The purpose of this study is to explore differences in retinal gene expression profiles between diseased and non-diseased rhesus monkeys.
Four affected monkeys and four unaffected monkeys, all >17 years of age, were selected based on formally-graded retinal photographs. At necropsy, enucleated eyes were dissected, and RNA extracted from a 4mm punch of macular neural retina was used for gene expression profiling with the Affymetrix Rhesus Macaque Genome Array, which provides comprehensive transcriptome coverage of the rhesus macaque genome (~52,000 assays). Fellow eyes were fixed in 4% paraformaldehyde for immunohistochemistry.
After background adjustment, quantile normalization and summarization using Robust Multichip Analysis, approximately 400 genes showed differential expression concordant among all affected samples, and approximately 50 met joint criteria of >1.5-fold change and p<0.05. The number of genes for which differential expression remained statistically significant depended upon adjustments for false discovery rate and the stringency of fold change criteria. Immunohistochemistry demonstrated that drusen in rhesus eyes shared the same molecular components as their human counterparts including the key markers of inflammation, vitronectin, C5b9 complement complex and ApoE.
These initial indications of differential gene expression in rhesus retinas will be confirmed with additional samples, qPCR and functional analysis as well as gene expression profiling of other retinal regions. Identifying gene expression differences in rhesus eyes with maculopathy lays the groundwork for better understanding of the molecular processes underlying macular disease in monkeys and its similarity with the human disease.
This PDF is available to Subscribers Only