VEGF is major stimulator in model of choroidal neovascularization

PURPOSE. Vascular endothelial growth factor (VEGF) is upregulated by hypoxi a and is a major stimulatory factor for retinal neovascularization in ische mic retinopathies such as diabetic retinopathy. This study sought to determ ine if VEGF is a stimulatory factor in a murine model of choroidal neovascu larization (CNV). METHODS. Mice with laser-induced ruptures in Bruch's membrane were treated with vehicle alone; a drug that inhibits both VEGF and platelet-derived gro wth factor (PDGF) receptor kinases; a drug that inhibits PDGF, but not VEGF receptor kinase; or genistein, a nonspecific kinase inhibitor. After two w eeks, CNV was quantified and compared. RESULTS. Blockade of phosphorylation by VEGF and PDGF receptors caused dram atic, almost complete inhibition of CNV. Genistein also had an inhibitory e ffect, but less so than the VEGF/PDGF receptor blocker. Blockade of phospho rylation by PDGF receptors, but not VEGF receptors, had no significant effe ct on CNV. CONCLUSIONS. These data and our previous study, which demonstrated that a k inase inhibitor that blocks VEGF and PDGF receptors and several isoforms of protein kinase C causing dramatic inhibition of CNV, suggest that VEGF sig naling plays a critical role in the development of CNV in this model. If sa fety is established, the effect of inhibiting VEGF receptor kinase activity should be investigated in patients with CNV.