CD36 Controls VEGF in Choroidal Neovascularization

Abstract

Purpose: : The multiple ligand receptor CD36 is the main anti-angiogenic receptor of thrombospondin-1 (TSP-1) on vascular endothelial cells. On the other hand, CD36 signalling induces proangiogenic COX-2 expression on RPE cells (Houssier et al. 08, PloS Medecine) and can be implicated in Macrophages/Microglial cell migration and activation. We here analyzed the overall effect of CD36 deficiency on choroidal neovascularization, its implication in macrophage recruitment and VEGF regulation in macrophages and RPE cells.

Methods: : CD36 knockout mice, were submitted to laser induced injury. Macrophage recruitment was analyzed at 4d and neovascularization at 14days in vivo. CD36 deficient macrophages and RPE cells from SHR rats (that express a non-functional CD36) and their control were stimulated (FA6 Ab) and VEGF protein expression was analyzed by Elisa.

Results: : CD36 invalidation inhibits choroidal neovascularization significantly. VEGF baseline expression was diminished in CD36 deficient RPE cells. CD36 stimulation increased VEGF expression in macrophages and RPE cells of control rats, but not SHR rats. CD36 deficiency had no impact on macrophage recruitment to the injury site.

Conclusions: : CD36 promotes choroidal neovascularization in vivo. A rôle of CD36 as an anti-angiogenic receptor on vascular endothelial cells is not predominant. CD36 is not involved in macrophage recruitment to the Laser injury site. On the other hand, CD36 induces VEGF expression in RPE and macrophages, which might account for the observed differences of choroidal neovascularization in CD36+/+ and -/- mice. In summary, CD36 is an upstream regulator of VEGF. It induces VEGF expression in laser induced injury and promotes choroidal neovascularization. CD36 might be a useful drugtarget to control VEGF expression and choroidal neovascularization.

Keywords: age-related macular degeneration • neovascularization • retinal pigment epithelium