Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies.
Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies.
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DOI：
10.1167/iovs.18-24882
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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
AMD是老年人法律的失明的主要原因，通过涉及人体组织和患者的多学科研究可以接近。AMD是一种血管代谢炎性疾病，其中两组细胞外沉积物，即软玻璃疣/基底线性存款（BLinD）和视网膜下玻璃疣样存款（SDD），赋予萎缩和新血管形成的终末期的风险。了解沉积物的形成方式可以为新的预防和治疗提供见解。BLinD和SDD分别与视锥细胞和视杆细胞的地形学对应关系表明，在高度进化的眼睛特异性生理学中，视网膜外细胞之间以及布鲁赫膜和视网膜下腔之间新实现的交换途径。本文综述了软性玻璃疣/BLinD，总结了一个主要的超微结构成分是大的载脂蛋白B，含E，富含胆固醇的脂蛋白分泌的视网膜色素上皮细胞（RPE），卸载不需要的脂质的饮食和外节起源，创造动脉粥样硬化样进展在subRPE基底层空间的证据。临床观察和RPE细胞培养系统结合联合收割机表明，当功能性RPE的分泌物通过穿过老化的Bruch膜-脉络膜毛细血管内皮的出口受损而在RPE下-基底层空间中回流时，形成软玻璃疣/BLinD。软性玻璃疣的生命周期包括生长、RPE在玻璃疣顶部的前迁移、然后塌陷和萎缩。在人类和动物模型中的概念验证研究表明，靶向“布鲁赫膜中的油溢出”提供了治疗早期AMD中的一个过程的希望，该过程是向两个终末期进展的基础。一个同伴的文章地址内的黄斑生物学软玻璃疣的前身。
AMD is a major cause of legal blindness in older adults approachable through multidisciplinary research involving human tissues and patients. AMD is a vascular-metabolic-inflammatory disease, in which two sets of extracellular deposits, soft drusen/basal linear deposit (BLinD) and subretinal drusenoid deposit (SDD), confer risk for end-stages of atrophy and neovascularization. Understanding how deposits form can lead to insights for new preventions and therapy. The topographic correspondence of BLinD and SDD with cones and rods, respectively, suggest newly realized exchange pathways among outer retinal cells and across Bruch's membrane and the subretinal space, in service of highly evolved, eye-specific physiology. This review focuses on soft drusen/BLinD, summarizing evidence that a major ultrastructural component is large apolipoprotein B,E-containing, cholesterol-rich lipoproteins secreted by the retinal pigment epithelium (RPE) that offload unneeded lipids of dietary and outer segment origin to create an atherosclerosis-like progression in the subRPE-basal lamina space. Clinical observations and an RPE cell culture system combine to suggest that soft drusen/BLinD form when secretions of functional RPE back up in the subRPE-basal lamina space by impaired egress across aged Bruch's membrane-choriocapillary endothelium. The soft drusen lifecycle includes growth, anterior migration of RPE atop drusen, then collapse, and atrophy. Proof-of-concept studies in humans and animal models suggest that targeting the “Oil Spill in Bruch's membrane” offers promise of treating a process in early AMD that underlies progression to both end-stages. A companion article addresses the antecedents of soft drusen within the biology of the macula.