Soluble VEGF Receptor-1 Restores Corneal Avascularity in Corn1 and Pax6+/- Mice

Abstract

Purpose:: We reported that soluble VEGF receptor-1 (sflt-1) expressed in corneal epithelium binds VEGF-A and maintains corneal avascularity. Although corn1 and Pax6^+/– mouse corneas are known to spontaneously vascularize, the underlying mechanisms are unclear. We studied corneal expression of sflt-1 in these mutant mice and in Pax6^+/– patients with aniridia associated neovascularization. We also tested the effect of exogenous sflt-1 administration on these mutant corneas.

Methods:: sflt-1 expression in the corneas of A/J, corn1, Pax6^+/+, and Pax6^+/– mice was determined by western blotting and in aniridic corneas by immunohistochemistry. sflt-1/Fc or IgG1-Fc protein was injected into the corneas of corn1 and Pax6^+/– mice. Cornea flat mounts were stained with CD31-FITC to detect blood vessels.

Results:: The avascular corneas of A/J and Pax6^+/+ mice expressed sflt-1 whereas corn1 and Pax6^+/– corneas did not. Enforced expression of recombinant sflt-1 restored corneal avascularity in these mutant mice. The corneas of patients with aniridia were deficient in sflt-1 compared to normal human corneas.

Conclusions:: Dysregulation of sflt-1 is involved in these models of spontaneous corneal neovascularization and administration of sflt-1 can be effective in treating this blinding condition.

Keywords: cornea: basic science • neovascularization