Center for Retina and Macular Disease, 250 Avenue K SW, Winter Haven, Fl 33880, USA.
Curr Mol Med. 2009 Nov;9(8):973-81. doi: 10.2174/156652409789712783.
The leading cause of blindness in the developed world results from several disorders that have pathologic ocular neovascularization as the common pathway leading to vision loss. These disorders include exudative age related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), retinal vein occlusions (RVO) and ocular tumors. Because neovascularization is the common pathway to blindness in these highly prevalent conditions, the recent understanding of the cascade of angiogenesis has led to clinically available molecular therapeutics that have been proven to restore and preserve vision in patients that suffer from these blinding conditions. This article will summarize the emergence of vascular endothelial growth factor (VEGF) as a validated treatment target for and current understanding of the pathophysiology of ocular neovascularization. The article will then cover promising future strategies and therapeutic targets that are aimed at enhancing the efficacy and/or duration of effect of these clinically available anti-VEGF strategies. In particular molecules that target, VEGF, PDGF, Complement, Inflammation and Integrins that are entering or are currently in clinical trials will be reviewed.
在发达国家,导致失明的主要原因是几种疾病,这些疾病都有眼部新生血管这一共同途径导致视力丧失。这些疾病包括渗出性年龄相关性黄斑变性(AMD)、糖尿病性视网膜病变(DR)、早产儿视网膜病变(ROP)、视网膜静脉阻塞(RVO)和眼部肿瘤。由于新生血管是这些高发疾病致盲的共同途径,最近对血管生成级联反应的认识导致了临床上可用的分子治疗药物,这些药物已被证明可恢复和维持患有这些致盲疾病的患者的视力。本文将总结血管内皮生长因子(VEGF)作为一个经过验证的治疗靶点的出现,以及对眼部新生血管形成的病理生理学的当前理解。然后,本文将介绍有前途的未来策略和治疗靶点,旨在提高这些临床可用的抗 VEGF 策略的疗效和/或作用持续时间。特别将综述针对 VEGF、PDGF、补体、炎症和整合素的分子,这些分子正在或已经进入临床试验。