Penn J S, Madan A, Caldwell R B, Bartoli M, Caldwell R W, Hartnett M E
Vanderbilt University School of Medicine, Nashville, TN, USA.
Prog Retin Eye Res. 2008 Jul;27(4):331-71. doi: 10.1016/j.preteyeres.2008.05.001. Epub 2008 May 28.
Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the US, for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.
总体而言，眼部血管生成性疾病是发达国家不可逆视力丧失的主要原因。例如，在美国，早产儿视网膜病变、糖尿病视网膜病变和年龄相关性黄斑变性分别是婴儿、工作年龄人群和老年人群失明的主要原因。有证据表明，血管内皮生长因子（VEGF），一种40kDa的二聚体糖蛋白，在上述每种疾病中均促进血管生成，使其成为一个极具意义的治疗靶点。然而，VEGF具有多效性，影响广泛的内皮、神经元和神经胶质细胞行为，并且混淆了抗VEGF策略的有效性，尤其是在慢性疾病状态下。事实上，在其他功能中，VEGF可在多种生物学环境中影响细胞增殖、细胞迁移、蛋白水解、细胞存活和血管通透性。本文将描述VEGF在早产儿视网膜病变、糖尿病视网膜病变和年龄相关性黄斑变性发病机制中所起的作用。还将讨论抑制VEGF的潜在弊端，以及靶向其他与VEGF相关的血管生成调节剂的基本原理。
