Netrin-4 mediates corneal neovascularization

Abstract

Purpose: Netrin-4, a secreted protein, regulates neuronal and vascular growth. It is found in the basement membranes of blood vessels. Previous results are contradictory supporting Netrin-4 as either a pro- or anti-angiogenic factor. In the presented study we investigated the role of Netrin-4 in the mouse-model of suture-induced, inflammatory corneal neovascularization.

Methods: Corneal neovascularization was induced in Netrin-4-deficient (Ntn4-/-) and wild-type mice by suturing three 11-0 nylon intrastromally into the cornea. Vascularized area of corneal flatmounts were analyzed 14 days after suturing by immunocytochemistry in conjunction withimage and statistical evaluation. The mRNA levels for VEGF-A and Netrin-4 in mouse corneas were analyzed by qPCR.

Results: In the wild-type mouse the netrin-4 expression was increased when corneal vascularization was increased by nylon saturation. Accordingly, Ntn4 -/- showed an increased corneal vascularized area compared to that in wild-type mice after suturing. Additionally, mRNA level of VEGF-A was increasedin Ntn4-/- compared to that in wild-type mice.

Conclusions: Netrin-4 probably acts as an anti-angiogenic factor through down-regulation of VEGF-A expression in the suture induced corneal neovascularization.

Keywords: 480 cornea: basic science • 609 neovascularization