A single local injection of recombinant VEGF receptor 2 but not of tie2 inhibits retinal neovascularization in the mouse

Purpose: The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia- induced proliferative retinopathy. Methods: C57BL/ 6J mice were placed in 76% oxygen on postnatal day 7 ( P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor ( sVEGF- R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein- dextran to quantify the retinopathy. Results: A single intravitreal injection of sVEGF- R2 reduced pathologic vascular changes significantly ( p = 0.02). No significant effect was observed after intravitreal application of sTie2 ( p = 0.07), although Ang- 2 was upregulated in control animals without treatment as neovascularization developed and Ang- 1 was constantly transcribed ( ratio PCR). Conclusions: sVEGF- R2 interferes with VEGF signaling via VEGF- R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy. Receptors with a wide range of ligands might prove more useful for local application than those binding few or antagonistic ligands.