This review provides a model for the role of oxidative stress in the etiology of age-related macular degeneration (AMD). Epidemiological studies of diet, environmental and behavioral risk factors suggest that oxidative stress is a contributing factor of AMD. Pathological studies indicate that damage to the retinal pigment epithelium (RPE) is an early event in AMD. In vitro studies show that oxidant treated RPE cells undergo apoptosis, a possible mechanism by which RPE cells are lost during early phase of AMD. The main target of oxidative injury seems to be mitochondria, an organelle known to accumulate genomic damages in other postmitotic tissues during aging. The thiol antioxidant GSH and its amino acid precursors protect RPE cells from oxidant-induced apoptosis. Similar protection occurs with dietary enzyme inducers which increase GSH synthesis. These results indicate that therapeutic or nutritional intervention to enhance the GSH antioxidant capacity of RPE may provide an effective way to prevent or treat AMD.
