The role of oxidative stress in the pathogenesis of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blind regist ration in the developed world, and yet its pathogenesis remains poorly unde rstood. Oxidative stress, which refers to cellular damage caused by reactiv e oxygen intermediates (ROI), has been implicated in many disease processes , especially age-related disorders. ROIs include free radicals, hydrogen pe roxide, and singlet oxygen, and they are often the byproducts of oxygen met abolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consi stently shown that photochemical retinal injury is attributable to oxidativ e stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipo fuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, t he relationships between dietary and serum levels of the, antioxidant vitam ins and age-related macular disease are less clear, although a protective e ffect of high plasma concentrations of a-tocopherol has been convincingly d emonstrated. Macular pigment is also believed to limit retinal oxidative da mage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, includi ng female gender, lens density, tobacco use, light iris color, and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced r isk of neovascular AMD. The concept that AMD can be attributed to cumulativ e oxidative stress is enticing, but remains unproven. With a view to reduci ng oxidative damage, the effect of nutritional antioxidant supplements on t he onset and natural course of ae-related macular disease is currently bein g evaluated. (C) 2000 by Elsevier Science Inc. All rights reserved.