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H. Cai, J. Gong, L. V. Del Priore; Comparison of Gene Expression Profiles From Young and Older Human Retinal Donor Eyes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3769.
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Age-related macular degeneration (AMD) is characterized by cellular changes in the RPE, choriocapillaris and retinal atrophy or choroidal neovascularization. Ultimately some changes in cellular behavior may be initiated by changes in the gene expression profile of the cells. A systematic comparison of the gene expression profiles of young versus older neural retina is thus important. Herein we use DNA microarray U133 Plus chip to determine the gene expression profiles of young and old, macular and peripheral retinae from human donor eyes.
Macular and peripheral neural retinae from six human donors (age: 21 to 81 years) were collected within 48 hours of death and total RNA was isolated. First and second strand cDNA were synthesized with a T7-(dT)24 oligomer for priming. Biotin-labeled antisense cRNA was produced by in vitro transcription. Target hybridization, washing, staining and scanning probe arrays were done following an Affymetrix GeneChip Expression Analysis Manual. Affymetrix GCOS Manager and Stratagene ArrayAssit software were used for data analysis.
Hierarchic clustering analysis of 12 samples demonstrates that the gene expression profiles of the young and older retina into two groups with little discernable overlap. The presence of about 27,000 probes (out of 54,000 probe set on microarray Human U133 Plus 2.0 array chip) was detected in all sample types. There are 70 gene probe sets present only in young macular but not detected in old macular retina; approximately 70 other distinct genes are expressed only in older macular retinae. The genes missing in older macula include genes known to be important for retinal survival/protection such as XIAP (X-linked inhibitor of apoptosis), Cadherin, PTK2 protein tyrosine kinase (PTK2), and a brain-derived neurotrophic factor (BDNF). Genes only present in older macula include nuclear receptor co-repressor 2 (NCOR2) and chloride intracellular channel 4 (CLIC4), known to be associated with aging/apoptosis in cells. Analysis of young and older peripheral retina shows there are 44 gene probes present in peripheral retinae from young donors but not in older donor peripheral samples while there are 82 gene probes only in the peripheral retinal samples from older donors.
There are major differences in macular retinal gene expression profiles of young vs. older donor eyes, and some genes known to be critical for retinal function/survival are not present within older macular retinae. Our study suggests that losing functions of those missing genes in macular retina with aging may be important in the development of AMD.
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