title: Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration.
abstract: Oxidative stress is believed to contribute to the pathogenesis of many diseases, including age-related macular degeneration (AMD). Although the vision loss of AMD results from photoreceptor damage in the central retina, the initial pathogenesis involves degeneration of RPE cells. Evidence from a variety of studies suggests that RPE cells are susceptible to oxidative damage. Mitochondrial DNA (mtDNA) is particularly prone to oxidative damage compared to nuclear DNA (nDNA). Using the quantitative PCR assay, a powerful tool to measure oxidative DNA damage and repair, we have shown that human RPE cells treated with H(2)O(2) or rod outer segments resulted in preferential damage to mtDNA, but not nDNA; and damaged mtDNA is not efficiently repaired, leading to compromised mitochondrial redox function as indicated by the MTT assay. Thus, the susceptibility of mtDNA to oxidative damage in human RPE cells, together with the age-related decrease of cellular anti-oxidant system, provides the rationale for a mitochondria-based model of AMD.
authors.affiliation: Retina Foundation of the Southwest, Anderson Vision Research Center, 9900 N. Central Expressway, Suite 400, Dallas, TX 75231, USA.
authors.forename: Fong-Qi
authors.initials: FQ
authors.lastname: Liang
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Godley
mesh_terms: D000375:Aging / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D010857:Pigment Epithelium of Eye / Q000473:pathology*
chemical_list: D004272:DNA, Mitochondrial