Novel approaches to corneal angiogenesis: macrophages, angiopoietin and VEGFs

Abstract

A transparent, avascular cornea is essential for proper vision. Ingrowth of neovessels follows severe ocular ailments such as injuries, infections, or autoimmune diseases. We report that TIE2-expressing monocytes (TEMs) -a specific macrophage population- is found in quiescent, avascular murine and human corneas and their number increases significantly during corneal neovascularization (CNV). We also found that Angiopoietin 2 (ANG2), a ligand of the TIE2 receptor, is abundantly and selectively expressed in the epithelium of quiescent murine and human corneas. Moreover, epithelial ANG2 diffuses into the corneal stroma upon injury, depending on its severity. Both TEMs and ANG2 are required for corneal neovascularization. CNV is reduced by selective depletion of TEMs or pharmacological blockade of ANG2. The recognition that TEMs and ANG2 promote CNV identifies them as relevant targets for the development of new therapies to modulate neovascularization.