Mechanisms of retinal angiogenesis

Studies of vessel growth in the retina have contributed to the understanding of retinal development and disease, and also to the establishment of principles of angiogenesis. The earliest formulation of the concept of a vasoformative factor, produced by a tissue to control its vascularisation, came from studies of vessel growth in developing retina, prompted by the clinical importance of neovascularising retinal disease. As in vitro techniques developed, a large number of factors-growth factor proteins, peptides, adhesion molecules and cytokines-were shown to be capable of promoting, facilitating or inhibiting the growth of vessels. This range of possible angiogenic factors was narrowed by subsequent in vivo studies of the retina, in particular studies of the pathogenesis of retinopathy or prematurity, a proliferative vasculopathy of developing retina. From these studies came the understanding that the level of oxygen in retinal tissue drives both normal development and neovascularising disease. This made clear that if there is a principal angiogenic factor which controls the growth of retinal vessels it must be hypoxia-inducible and led to investigation of the role of vascular endothelial growth factor (VEGF) in retinal angiogenesis. VEGF was first identified as a potent and specific angiogenic factor less than a decade ago. When its expression was shown in tumour models to be hypoxia-inducible, studies followed which showed that VEGF has the properties and is expressed in the retina in spatial and temporal patterns which indicate that it plays key role in the induction of normal vessel growth, in the maintenance of vessels once formed and in the induction of neovascularising disease of the retina. Future work will explore the interaction of VEGF with other angiogenic molecules and will explore the therapeutic potential of controlling the expression and secretion of VEGF by the retina, and of enhancing or blocking the binding of VEGF to its receptors. Copyright (C) 1997 Elsevier Science Ltd.