Vascular endothelial growth factors and angiogenesis in eye disease

被引:789
作者
Witmer, AN
Vrensen, GFJM
Van Noorden, CJF
Schlingemann, RO
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Ocular Angiogenesis Grp, NL-1100 DD Amsterdam, Netherlands
[2] Leiden Univ, Med Ctr, Dept Ophthalmol, Leiden, Netherlands
[3] Univ Amsterdam, Acad Med Ctr, Dept Histol & Cell Biol, NL-1100 DD Amsterdam, Netherlands
关键词
vascular endothelial growth factors; endothelial growth factor receptors; angiogenesis; vascular permeability; endothelial cells; pericytes; tissue distribution; eye; diabetic retinopathy; age-related macular degeneration;
D O I
10.1016/S1350-9462(02)00043-5
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
The vascular endothelial growth factor (VEGF) family of growth factors controls pathological angiogenesis and increased vascular permeability in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). The purpose of this review is to develop new insights into the cell biology of VEGFs and vascular cells in angiogenesis and vascular leakage in general, and to provide the rationale and possible pitfalls of inhibition of VEGFs as a therapy for ocular disease. From the literature it is clear that overexpression of VEGFs and their receptors VEGFR-1, VEGFR-2 and VEGFR-3 is causing increased microvascular permeability and angiogenesis in eye conditions such as DR and AMD. When we focus on the VEGF receptors, recent findings suggest a role of VEGFR-1 as a functional receptor for placenta growth factor (PIGF) and vascular endothelial growth factor-A (VEGF)-A in pericytes and vascular smooth muscle cells in vivo rather than in endothelial cells, and strongly suggest involvement of pericytes in early phases of angiogenesis. In addition, the evidence pointing to distinct functions of VEGFs in physiology in and outside the vasculature is reviewed. The cellular distribution of VEGFR-1, VEGFR-2 and VEGFR-3 suggests various specific functions of the VEGF family in normal retina, both in the retinal vasculature and in neuronal elements. Furthermore, we focus on recent findings that VEGFs secreted by epithelia, including the retinal pigment epithelium (RPE), are likely to mediate paracrine vascular survival signals for adjacent endothelia. In the choroid, derailment of this paracrine relation and overexpression of VEGF-A by RPE may explain the pathogenesis of subretinal neovascularisation in AMD. On the other hand, this paracrine relation and other physiological functions of VEGFs may be endangered by therapeutic VEGF inhibition, as is currently used in several clinical trials in DR and AMD. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
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页码:1 / 29
页数:29
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