Delayed inflammation-associated corneal neovascularization in MMP-2-deficient mice.

Abstract

Corneal neovascularization is a significant, sight-threatening, complication of many ocular surface disorders, but its underlying molecular background is still not fully understood. In the present study, we analysed the expression and role of matrix metalloproteinase-2 (MMP-2), a proteolytic enzyme suggested to regulate angiogenesis, in a mouse model of inflammation-related corneal neovascularization. A silk suture was placed centrally in pigmented mice corneas causing limbal vasculature to sprout, forming new vessels. Neovascularization progressed centrally involving the entire cornea after about 12 days. Histological analysis revealed vascularization of the corneal stroma accompanied by a marked inflammatory response. The neovascularization correlated with an increased expression of MMP-2 mRNA and protein that was mainly found in cells that stained positively for S100A4, a marker for activated keratocytes. MMP-2-deficient mice and wild-type mice were compared in a kinetic study, showing a statistically significant delay of neovascularization in MMP-2-deficient mice. These results implicate a role for MMP-2 in experimental inflammation-associated corneal neovascularization.