Farnoodian Mitra, Wang Shoujian, Dietz Joel, Nickells Robert W, Sorenson Christine M, Sheibani Nader
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, U.S.A.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, U.S.A.
Clin Sci (Lond). 2017 Jul 5;131(15):1763-1780. doi: 10.1042/CS20170066. Print 2017 Aug 1.
Angiogenesis contributes to the pathogenesis of many diseases including exudative age-related macular degeneration (AMD). It is normally kept in check by a tightly balanced production of pro- and anti-angiogenic factors. The up-regulation of the pro-angiogenic factor, vascular endothelial growth factor (VEGF), is intimately linked to the pathogenesis of exudative AMD, and its antagonism has been effectively targeted for treatment. However, very little is known about potential changes in expression of anti-angiogenic factors and the role they play in choroidal vascular homeostasis and neovascularization associated with AMD. Here, we will discuss the important role of thrombospondins and pigment epithelium-derived factor, two major endogenous inhibitors of angiogenesis, in retinal and choroidal vascular homeostasis and their potential alterations during AMD and choroidal neovascularization (CNV). We will review the cell autonomous function of these proteins in retinal and choroidal vascular cells. We will also discuss the potential targeting of these molecules and use of their mimetic peptides for therapeutic development for exudative AMD.
血管生成参与包括渗出性年龄相关性黄斑变性（AMD）在内的多种疾病的发病机制。它通常通过促血管生成因子和抗血管生成因子的紧密平衡产生来维持平衡。促血管生成因子血管内皮生长因子（VEGF）的上调与渗出性AMD的发病机制密切相关，其拮抗作用已成为有效的治疗靶点。然而，对于抗血管生成因子表达的潜在变化及其在与AMD相关的脉络膜血管稳态和新生血管形成中所起的作用，我们知之甚少。在此，我们将讨论血小板反应蛋白和色素上皮衍生因子这两种主要的内源性血管生成抑制剂在视网膜和脉络膜血管稳态中的重要作用，以及它们在AMD和脉络膜新生血管形成（CNV）过程中的潜在变化。我们将回顾这些蛋白在视网膜和脉络膜血管细胞中的细胞自主功能。我们还将讨论这些分子的潜在靶向作用以及使用它们的模拟肽进行渗出性AMD治疗开发的情况。
