Macrophage Mediated VEGF Expression in Ocular Angiogenesis

Abstract

Purpose: : The most severe pathology of eye disease is the formation of retinal and choroidal neovascularization. Still, the discussion of a primary role of inflammation versus a secondary cause of retinal neovascularization is not solved. VEGF is the most prominent growth factor in ocular angiogenesis. The aim of this study was to investigate the role of VEGF secretion by macrophages to retinal angiogenesis.

Methods: : To induce retinal neovascularization macrophage-specific VEGF deficient mice (KO) and the respective wild type (WT) mice were used. The nursing dam and her pups were exposed to 75% oxygen at postnatal day 7 to 12 and then transferred back to room air. Retinal neovascularization was assessed on retinal flatmounts after labeling of the blood vessels with isolectin IB4. Pathological infiltration with inflammatory cells was investigated by immunocytochemistry. Cell apoptosis was examined by TUNEL assays on paraffin sections. Western blot was performed to quantify active caspase-3, caspase-8 and VEGF protein expression.

Results: : There was no difference in the number and localization of neovascular tufts or avascular area between KO and WT mice on retinal flatmounts. Similarly, there was no difference in macrophage infiltration and apoptotic cells. Total retinal VEGF expression did not differ among the groups.

Conclusions: : These results indicate that compensatory factors may trigger the formation of retinal neovascularization when VEGF secretion by macrophages is inhibited. The role of macrophages and its interaction with e.g. VEGF expressing Mueller cells needs warrants further investigation.

Keywords: vascular endothelial growth factor • neovascularization • hypoxia