Agostini H T, Hansen L L
Universitäts-Augenklinik Freiburg.
Ophthalmologe. 2003 May;100(5):371-7. doi: 10.1007/s00347-003-0801-7.
Ischemia is a major stimulus for angiogenesis, a biological response mechanism that describes the formation of new blood vessels from existing vessels. An ischemic cell communicates with endothelial cells by soluble factors such as VEGF (vascular endothelial growth factor) and its receptors. A major transcriptional factor for VEGF is HIF-1 (hypoxia inducible factor). Proliferation of endothelial cells alone does not result in stable vascular tubes, this is only achieved by recruiting additional cells such as pericytes. The stabilisation and destabilisation of vessels, which are important prerequisites for vascular growth, are in a dynamic equilibrium which can be modified by additional growth factors such as angiopoietins. In this review we discuss some of the molecular mechanisms leading from ischemia to proliferative retinopathy with a special focus on retinopathy of prematurity and the closely related mouse model of hyperoxia-induced retinopathy. This model is very useful when developing new antiangiogenic therapies based on the increasing understanding of the molecular pathogenesis of ischemic proliferative retinopathy.
缺血是血管生成的主要刺激因素，血管生成是一种生物学反应机制，描述了从现有血管形成新血管的过程。缺血细胞通过诸如血管内皮生长因子（VEGF）及其受体等可溶性因子与内皮细胞进行通讯。VEGF的一个主要转录因子是缺氧诱导因子1（HIF-1）。仅内皮细胞的增殖不会产生稳定的血管管，这只有通过募集额外的细胞（如周细胞）才能实现。血管的稳定和不稳定是血管生长的重要前提，它们处于动态平衡中，这种平衡可被诸如血管生成素等其他生长因子所改变。在本综述中，我们讨论了一些从缺血到增殖性视网膜病变的分子机制，特别关注早产儿视网膜病变以及与之密切相关的高氧诱导视网膜病变小鼠模型。当基于对缺血性增殖性视网膜病变分子发病机制的日益了解来开发新的抗血管生成疗法时，该模型非常有用。
