Progressive RPE dysfunction and death cause a secondary degeneration of rods and cones.This may be due to the close interaction between the RPE and photoreceptor cells in both nutritional and metabolic processes.Among the environmental factors, exposure to sunlight and cigarette smoking have been linked to the risk of AMD development. Intense illumination or toxic compounds in the tobacco smoke can induce generation of reactive oxygen species, thus leading to increased purchase Digoxigenin oxidative stress.The nutritional risk factor involves low dietary intake of antioxidants. Increased dietary intake and serum levels of specic antioxidant nutrients may reduce the risk for AMD. The linkage between antioxidant micronutrients and AMD was further strengthened by the AREDS clinical trial results which demonstrated a signicant reduction in the rate of AMD progression in subjects taking antioxidant and zinccontaining supplements. Several studies have suggested that there may be a genetic linkage in AMD epidemiology.A higher prevalence was found between monozygotic twins and among the rstdegree relatives with AMD. The genetic risk for AMD has been recently estimated as only. Thus, the genetic contribution to AMD, although important, appears to be minor compared to environmental factors.Most of the known risk factors for AMD such as environmental and nutritional factors appear to have oxidative stress as a common denominator. We hypothesize that chronic oxidative stress causes molecular and cellular damage in susceptible RPE cells, which in turn may lead to the pathological and clinical ndings seen with AMD.In this review article we provide current information on oxidative stress induced DNA damage and repair in the human RPE cells, with specic emphasis on the mitochondrial DNA.ROS are produced by a variety of pathways of aerobic metabolism; however, the major source of their production is the mitochondria.Mitochondrial oxidative phosphorylation is a powerful source of ROS with up to of the oxygen picking up electrons directly from the avin dehydrogenases and ubiquinol to generate superoxide radicals. Being a major producer of ROS, mitochondria may thus be subjected to direct attack of ROS.Thus, mtDNA damage is a good biomarker of oxidative stress.Cellular lipids and proteins can also be damaged by ROS, such as lipid peroxidation. Lipid peroxidation may stimulate secondary ROS reactions due to electrophiles generated within the mitochondrial membrane.Secondary reactive oxygen reactions may then lead to continued mtDNA damage due to its position on the matrix side of the inner membrane.Since mtDNA encodes proteins involved in electron transport, mtDNA damage will lead to a decrease in mt mRNA and protein synthesis.Because mitochondrial respiration is essential for the production of ATP, damage to mitochondria as a result of oxidative stress could result in reduced energy production and compromised cell function.Over time, decits in cellular function caused by this cycle of oxidative damage could become amplied and contribute to agerelated declines in physiological function.Damage to mtDNA probably has more relevance to the mitochondrial theory of aging than damage to lipid or protein because mtDNA damage can be propagated as mitochondria and cells divide, thus allowing the physiological consequences of the damage to be amplied.This close location exposes RPE cells to a highly oxidative environment due to high oxygen partial pressure from the underlying choriocapillaries.