This review provides a model for the role of oxidative stress in the etiolo
gy of age-related macular degeneration (AMD). Epidemiological studies of di
et, 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 t
arget of oxidative injury seems to be mitochondria, an organelle known to a
ccumulate genomic damages in other postmitotic tissues during aging. The th
iol antioxidant GSH and its amino acid precursors protect RPE cells from ox
idant-induced apoptosis. Similar protection occurs with dietary enzyme indu
cers 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. (C) 2000 Elsevier Sci
ence Ltd. All rights reserved.