The role of antioxidants in the retina and retinal pigment epithelium and the nature of prooxidant-induced damage

The vertebrate retina has several features that make it vulnerable to damage from autoxidation. The photoreceptor membranes contain high levels of polyunsaturated fatty acids; abundant mitochondria are present which may leak activated oxygen species; and light exposure of the retina may cause photoxidation. These features are analyzed in detail, and the various antioxidant mechanisms of the vertebrate retina are surveyed. The interplay among oxidant stress and antioxidant defenses is illustrated by review of situations where these variables are either artificially manipulated or changed naturally. Vitamin E deficiency damages the retina in a number of well-defined vertebrate model systems, and a lipid autoxidation mechanism for this damage is widely assumed. The retina is quite sensitive to damage by elevated or prolonged light exposure; however, a free-radical role in light damage to the retina has not been established. An alternative mechanism for damage due to vitamin E deficiency and light is considered, which involves elevated vitamin A levels and vitamin A toxicity. Evidence is reviewed that the primate retina requires both vitamin E and selenium. The puzzling role of ocular melanin in light damage and protection is reviewed. Possible contributions of autoxidative damage to aging of the human retina are discussed.