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H. Cai, L.V. Del Priore; ATP Binding Cassette (ABC) Gene Expression Within Human RPE: Evidence That ABCC5 Is Downregulated by Aging of Human Bruch’s Membrane . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3061.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: ABC transporter genes have been implicated in the pathogenesis of several retinal degenerations. The purpose of this study is to determine the expression level of members of the ABC gene superfamily in adult human RPE (ahRPE) and spontaneously immortalized RPE (ARPE19) and the effects of Bruch’s membrane aging on expression of these ATP–dependent membrane transporters. Methods: ahRPE and ARPE19 cells were seeded onto human Bruch’s membrane from younger (<age 50) and older (>age 70) donors. RPE were harvested 72 hours later and total RNA was isolated using standard techniques. The RPE gene expression profile was determined using the Affymetrix Human 95UA gene chip; we calculated the expression ratio on old vs. young Bruch’s membrane for each gene. Data were analyzed with DNA microarray analysis software. Results: The Affymetrix chip contains a total of 69 genes within the ABC transporter superfamily; we were able to detect the expression of 21 of these genes in ahRPE and 21 genes within ARPE19, with 100 % overlap in the expression profile. Bruch’s membrane aging downregulates ABCC5 in ARPE19 and ahRPE (old/young = 0.5 and 0.75; p= 0.006 and 0.03, respectively). One additional gene (ATP–binding cassette, sub–family B) was upregulated on older Bruch’s membrane in ahRPE (p = 0.027) but not ARPE19. Conclusions: Members of the ABC gene superfamily are expressed within adult human RPE and an immortalized cell line. ABCC5, a member of the human ABC gene superfamily that encodes for ATP binding cassettes involved in transmembrane transport of cyclic nucleotides and cholesterol, was consistently downregulated with Bruch’s membrane aging in ahRPE and ARPE19. Downregulation of ABCC5 with Bruch’s membrane aging may decrease clearance of these substances and increase intracellular cGMP. Further work is needed to elucidate the effects of alterations in ABCC5 of the cell biology of the RPE and adjacent tissues.
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