Negative regulators of angiogenesis: important targets for treatment of exudative AMD.
Negative regulators of angiogenesis: important targets for treatment of exudative AMD.
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DOI：
10.1042/cs20170066
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发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Sheibani N
中科院分区：
文献类型：
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作者：
Farnoodian M;Wang S;Dietz J;Nickells RW;Sorenson CM;Sheibani N
血管生成导致许多疾病的发病机制，包括渗出性年龄相关性黄斑变性（AMD）。它通常通过促血管生成因子和抗血管生成因子的严格平衡产生来控制。促血管生成因子血管内皮生长因子的上调与渗出性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，人们对抗血管生成因子表达的潜在变化及其在脉络膜血管稳态和与 AMD 相关的新血管形成中所起的作用知之甚少。在这里，我们将讨论血小板反应蛋白和色素上皮衍生因子（血管生成的两种主要内源性抑制剂）在视网膜和脉络膜血管稳态中的重要作用及其在 AMD 和脉络膜新生血管形成过程中的潜在变化。我们将回顾这些蛋白质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以及它们的模拟肽在渗出性 AMD 治疗开发中的用途。
Angiogenesis contributes to 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 proangiogenic factor, vascular endothelial growth factor, 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 antiangiogenic 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. 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.