Oxidative damage and age-related macular degeneration.
Oxidative damage and age-related macular degeneration.
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DOI：
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发表时间：
1999-11
期刊：
影响因子：
2.2
通讯作者：
B. S. Winkler;M. Boulton;J. Gottsch;P. Sternberg
中科院分区：
文献类型：
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作者：
B. S. Winkler;M. Boulton;J. Gottsch;P. Sternberg
这篇文章提供了有关氧化在老年性黄斑变性（AMD）中潜在作用的最新信息。重点是氧化剂和自由基的产生以及抗氧化剂在视网膜外的保护作用，特别强调光感受器细胞、视网膜色素上皮和绒毛膜毛细血管。起点包括讨论和定义自由基是什么，它们的内源性来源，它们如何反应，以及它们可能造成的损害。光感受器/色素上皮复合体暴露在阳光下，沐浴在接近动脉水平的氧气中，该复合体的膜含有高浓度的多不饱和脂肪酸，这些都被认为是导致氧化损伤的潜在因素。本文讨论了抗氧化剂如谷胱甘肽、维生素C、超氧化物歧化酶、过氧化氢酶、维生素E和类胡萝卜素在预防氧化损伤中的作用。脂褐素是一组复杂的自荧光脂/蛋白聚集物，聚集在视网膜色素上皮中，它的光毒性被描述，并且有证据表明细胞内脂褐素对这些细胞有毒性，因此支持脂褐素在衰老和AMD中的作用。AMD主要是由于绒毛膜毛细血管光敏性损伤的理论被评估。结果表明，当原畸形小鼠暴露在蓝光下时，绒毛膜毛细血管内皮诱导IV型胶原合成，导致布鲁氏膜增厚，并出现视网膜下色素上皮纤维颗粒沉积，类似于基底层流沉积。AMD可能由视网膜色素上皮氧化损伤引起的假设在实验中得到进一步评估，实验旨在测试谷胱甘肽在防止暴露于氧化剂的培养的人类色素上皮细胞损伤方面的保护作用。利用富马酸二甲基（一种单功能诱导剂）增加色素上皮细胞中谷胱甘肽浓度的实验，描述了这些细胞在氧化挑战中存活的能力。虽然所有这些模型都提供了无可争议的证据，证明视网膜色素上皮和绒毛膜毛细血管的氧化损伤是光依赖性和氧依赖性的，但目前尚不清楚氧化诱导事件与AMD的发生和进展之间的确切联系。
This article provides current information on the potential role of oxidation in relation to age-related macular degeneration (AMD). The emphasis is placed on the generation of oxidants and free radicals and the protective effects of antioxidants in the outer retina, with specific emphasis on the photoreceptor cells, the retinal pigment epithelium and the choriocapillaris. The starting points include a discussion and a definition of what radicals are, their endogenous sources, how they react, and what damage they may cause. The photoreceptor/pigment epithelium complex is exposed to sunlight, is bathed in a near-arterial level of oxygen, and membranes in this complex contain high concentrations of polyunsaturated fatty acids, all considered to be potential factors leading to oxidative damage. Actions of antioxidants such as glutathione, vitamin C, superoxide dismutase, catalase, vitamin E and the carotenoids are discussed in terms of their mechanisms of preventing oxidative damage. The phototoxicity of lipofuscin, a group of complex autofluorescent lipid/protein aggregates that accumulate in the retinal pigment epithelium, is described and evidence is presented suggesting that intracellular lipofuscin is toxic to these cells, thus supporting a role for lipofuscin in aging and AMD. The theory that AMD is primarily due to a photosensitizing injury to the choriocapillaris is evaluated. Results are presented showing that when protoporphyric mice are exposed to blue light there is an induction in the synthesis of Type IV collagen synthesis by the choriocapillary endothelium, which leads to a thickened Bruch's membrane and to the appearance of sub-retinal pigment epithelial fibrillogranular deposits, which are similar to basal laminar deposits. The hypothesis that AMD may result from oxidative injury to the retinal pigment epithelium is further evaluated in experiments designed to test the protective effects of glutathione in preventing damage to cultured human pigment epithelial cells exposed to an oxidant. Experiments designed to increase the concentration of glutathione in pigment epithelial cells using dimethylfumarate, a monofunctional inducer, are described in relation to the ability of these cells to survive an oxidative challenge. While all these models provide undisputed evidence of oxidative damage to the retinal pigment epithelium and the choriocapillaris that is both light- and oxygen-dependent, it nevertheless is still unclear at this time what the precise linkage is between oxidation-induced events and the onset and progression of AMD.