A Single Local Injection of Recombinant VEGF Receptor 2 But Not of Tie2 Inhibits Retinal Neovascularization in the Mouse

Abstract

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.

KEYWORDS:

• angiopoietin
• oxygen-induced retinopathy
• receptor
• therapy
• VEGF