Mechanisms of age-related macular degeneration.
Mechanisms of age-related macular degeneration.
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DOI：
10.1016/j.neuron.2012.06.018
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发表时间：
2012-07-12
期刊：
影响因子：
16.2
通讯作者：
Fowler BJ
中科院分区：
文献类型：
--
作者：
Ambati J;Fowler BJ
视网膜相关性黄斑变性（AMD）是一种在高达90%的患者中无法治疗的进行性病症，是全球老年人失明的主要原因。两种形式的AMD，湿性和干性，分别基于已经破坏性侵入视网膜的血管的存在或不存在来分类。对湿性AMD潜在的分子机制的详细理解导致了几种强大的FDA批准的疗法。相比之下，没有任何批准的干性AMD治疗方法。在这篇综述中，我们提供了深入了解介导每种形式的疾病的关键效应途径。湿性AMD的免疫和血管系统的相互作用，以及对寻找基因变异来解释AMD发病机制的兴趣越来越大，这些都是在最新的临床和实验数据的背景下进行的。介绍了干性AMD发病机制的新模型，重点关注DICER 1缺陷和视网膜碎片的毒性积聚。跨越AMD发病机制的大多数方面的反复出现的主题是经典免疫特权眼部避风港中的免疫调节缺陷。有趣的是，AMD研究的最新进展突出了与其他常见神经退行性疾病共同的分子疾病途径。最后，干预AMD发病机制的治疗潜力进行了讨论。
Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed.
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