[Pathogenesis and prophylaxis of AMD: focus on oxidative stress and antioxidants]

Abstract

Age-related macular degeneration (AMD) is the leading cause of severe visual loss and blindness in people over 55. Its pathogenesis--likely multifactorial, involving a complex interaction of metabolic, functional, genetic and environmental factors--remains poorly understood. Among molecular links in pathogenesis of AMD is the oxidative stress in the retina, a structure that is particularly susceptible to damage by reactive oxygen species (ROS) since photoreceptor outer segment (POS) membranes are rich in polyunsaturated fatty acids which can be readily oxidized and can initiate a cytotoxic chain reaction. Occurring in the neighborhood of photoreceptors, the retinal pigment epithelial cells (RPE) actively contribute to both the retinoid cycle and catabolism of constantly shed and phagocytized parts of photoreceptor outer segments. Enzymatic degradation of photoreceptor fragments occurring in RPE phagolysosomes is not complete and undigested material in the form of insoluble aggregates, called lipofuscin, is deposited in lysosomes of RPE cells. Lipofuscin contains a mixture of diverse molecular components including retinoid-derived compounds, some of which displaying potent photoinducible properties, contributing to an enhancement and propagation of the oxidative stress. The retina possesses defense mechanisms against the oxidative stress that effectively neutralize the consequences of reactive oxygen species actions under normal conditions. A key role in the antioxidant defense plays an array of substances, including: xanthophylls (lutein and zeaxanthin), vitamin C and E, and glutathione. This paper surveys the current concepts on the role of the oxidative stress in pathophysiology of AMD, and describes major components of the antioxidant defense system, including their use in AMD prophylaxis and therapy.