Antecedents of Soft Drusen, the Specific Deposits of Age-Related Macular Degeneration, in the Biology of Human Macula.
Antecedents of Soft Drusen, the Specific Deposits of Age-Related Macular Degeneration, in the Biology of Human Macula.
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DOI：
10.1167/iovs.18-24883
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发表时间：
2018-03-20
影响因子：
4.4
通讯作者：
Curcio CA
中科院分区：
文献类型：
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作者：
Curcio CA
最近在视网膜下间隙、光感受器和视网膜色素上皮(RPE)之间发现了含有细胞外胆固醇的沉积物，称为视网膜下色素沉淀物(SDDS)，这一发现不可逆转地改变了AMD的病理生物学。SDDS惊人地反映了人类黄斑中杆状感光细胞的地形，提出了一个问题：是否有一个相同的过程导致了与中心凹视锥有关的沉积。在此，我们认为AMD的病理性病变-软性玻璃体和基底线状沉积(盲目，相同的物质，弥漫分布)-是首选。流行病学、临床和组织学数据表明，这些沉积物在中央黄斑中心凹下最为丰富。一篇配套文章中提出的强有力的证据支持这一观点，即占主导地位的超微结构成分是由RPE结构性分泌的大载脂蛋白B，即含E的脂蛋白。脂蛋白脂肪酸主要由亚油酸盐(与饮食有关)而不是二十二碳六烯酸(与光感受器有关)主导；我们在视网膜内寻找细胞关系和饮食驱动因素来解释软德鲁兹的地形。通过RPE将叶黄素色素输送到高度进化的人类中心凹中的大量Müler细胞是一个强有力的候选方案，因为Müler细胞是这些色素的主要储存库，这些色素从饮食中补充。我们认为，神经胶质细胞关系和叶黄素递送的进化是以人类微妙的中心凹视觉为基础的，这是有代价的，即软玻璃体和后遗症，在我们的生殖年龄之后很久。
AMD pathobiology was irreversibly changed by the recent discovery of extracellular cholesterol-containing deposits in the subretinal space, between the photoreceptors and retinal pigment epithelium (RPE), called subretinal drusenoid deposits (SDDs). SDDs strikingly mirror the topography of rod photoreceptors in human macula, raising the question of whether an equivalent process results in a deposition related to foveal cones. Herein we propose that AMD's pathognomonic lesion—soft drusen and basal linear deposit (BLinD, same material, diffusely distributed)—is the leading candidate. Epidemiologic, clinical, and histologic data suggest that these deposits are most abundant in the central macula, under the fovea. Strong evidence presented in a companion article supports the idea that the dominant ultrastructural component is large apolipoprotein B,E–containing lipoproteins, constitutively secreted by RPE. Lipoprotein fatty acids are dominated by linoleate (implicating diet) rather than docosahexaenoate (implicating photoreceptors); we seek within the retina cellular relationships and dietary drivers to explain soft druse topography. The delivery of xanthophyll pigments to highly evolved and numerous Müller cells in the human fovea, through RPE, is one strong candidate, because Müller cells are the main reservoir of these pigments, which replenish from diet. We propose that the evolution of neuroglial relations and xanthophyll delivery that underlie exquisite human foveal vision came with a price, that is, soft drusen and sequela, long after our reproductive years.