Das Arup, McGuire Paul G
School of Medicine, University of New Mexico, Albuquerque, USA.
Prog Retin Eye Res. 2003 Nov;22(6):721-48. doi: 10.1016/j.preteyeres.2003.08.001.
Retinal angiogenesis and choroidal angiogenesis are major causes of vision loss, and the pathogenesis of this angiogenesis process is still uncertain. However, several key steps of the angiogenic cascade have been elucidated. In retinal angiogenesis, hypoxia is the initial stimulus that causes up regulation of growth factors, integrins and proteinases, which result in endothelial cell proliferation and migration that are critical steps in this process. Once the endothelial tube is formed from the existing blood vessels, maturation starts with recruitment of mural cell precursors and formation of the basement membrane. Normally, there is a tight balance between angiogenic factors and endogenous angiogenesis inhibitors that help to keep the angiogenic process under control. Although the steps of choroidal angiogenesis seem to be similar to those of retinal angiogenesis, there are some major differences between these two processes. Several anti-angiogenic approaches are being developed in animal models to prevent ocular angiogenesis by blocking the key steps of the angiogenic cascade. Based on these pre-clinical studies, several anti-angiogenic clinical trials are ongoing in patients with diabetic retinopathy and age-related macular degeneration. This review discusses the pathogenesis of retinal and choroidal angiogenesis, and alternative pharmacological approaches to inhibit angiogenesis in ocular diseases.
视网膜血管生成和脉络膜血管生成是导致视力丧失的主要原因，而这种血管生成过程的发病机制仍不明确。然而，血管生成级联反应的几个关键步骤已得到阐明。在视网膜血管生成中，缺氧是最初的刺激因素，它会导致生长因子、整合素和蛋白酶的上调，进而引起内皮细胞增殖和迁移，这些都是该过程中的关键步骤。一旦内皮管从现有的血管形成，成熟过程便随着壁细胞前体的募集和基底膜的形成而开始。正常情况下，血管生成因子与内源性血管生成抑制剂之间存在紧密平衡，有助于控制血管生成过程。尽管脉络膜血管生成的步骤似乎与视网膜血管生成相似，但这两个过程之间存在一些主要差异。目前正在动物模型中开发几种抗血管生成方法，通过阻断血管生成级联反应的关键步骤来预防眼部血管生成。基于这些临床前研究，针对糖尿病性视网膜病变和年龄相关性黄斑变性患者的多项抗血管生成临床试验正在进行。本文综述了视网膜和脉络膜血管生成的发病机制，以及抑制眼部疾病中血管生成的替代药理学方法。
