Wiktorowska-Owczarek Anna, Nowak Jerzy Z
Zakład Farmakologii, Katedra Farmakologii i Farmakologii Klinicznej Uniwersytetu Medycznego w Łodzi, 90-752 Łódź.
Postepy Hig Med Dosw (Online). 2010 Jul 28;64:333-43.
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.
年龄相关性黄斑变性（AMD）是55岁以上人群严重视力丧失和失明的主要原因。其发病机制可能是多因素的，涉及代谢、功能、遗传和环境因素的复杂相互作用，目前仍知之甚少。AMD发病机制中的分子联系之一是视网膜中的氧化应激，视网膜结构特别容易受到活性氧（ROS）的损伤，因为光感受器外段（POS）膜富含多不饱和脂肪酸，这些脂肪酸很容易被氧化，并能引发细胞毒性连锁反应。视网膜色素上皮细胞（RPE）位于光感受器附近，积极参与视黄醛循环以及对光感受器外段不断脱落和吞噬部分的分解代谢。在RPE吞噬溶酶体中发生的光感受器碎片的酶促降解并不完全，未消化的物质以不溶性聚集体的形式（称为脂褐素）沉积在RPE细胞的溶酶体中。脂褐素包含多种分子成分的混合物，包括视黄醛衍生的化合物，其中一些具有强大的光诱导特性，有助于氧化应激的增强和传播。视网膜具有针对氧化应激的防御机制，在正常情况下能有效中和活性氧作用的后果。一系列物质在抗氧化防御中起关键作用，包括：叶黄素（叶黄素和玉米黄质）、维生素C和E以及谷胱甘肽。本文综述了氧化应激在AMD病理生理学中的作用的当前概念，并描述了抗氧化防御系统的主要成分，包括它们在AMD预防和治疗中的应用。
