Ocular neovascularisation and excessive vascular permeability

Abstract

Diseases complicated by vascular leakage and/or neovascularisation in the eye are responsible for the vast majority of visual morbidity and blindness in developed countries. The molecular signals that control vascular permeability and neovascularisation in the eye are being defined. Members of the vascular endothelial growth factor (VEGF) family are key stimulators that interact with two tyrosine kinase receptors, VEGF receptor (VEGFR)1 and 2; binding to two other receptors that lack tyrosine kinase activity, the neuropilins, is also important. Signalling through the VEGF pathway is modulated by the Tie2 receptor and its binding partners, the angiopoietins. Each of the participants in these two signalling pathways provides a potential target for intervention. Several proteins with antiangiogenic activity balance the stimulators and the outcome is determined by the net balance. Endostatin suppresses vascular permeability as well as ocular neovascularisation, suggesting that vascular leakage may also be regulated by counteracting proteins. Gene transfer provides a useful way to influence these balances. Clinical trials are underway to test whether these mechanisms can be translated into new therapies.