Reduced retinal angiogenesis in MMP–2 deficient mice

Abstract

Abstract: : Purpose: To study the putative role of endogenous matrix metalloproteinases (MMPs) in retinal neovascularization, we used an established mouse model to compare the retinal neovascularization observed in wild–type mice to that in mice lacking the MMP–2 or MMP–9 gene. Methods: C57Bl/6 (MMP–2+/+, MMP–9+/+), MMP–2–deficient (MMP2–/–), and MMP–9–deficient (MMP–9–/–) mice were used. After oxygen–induced retinopathy was induced in the mice, their eyes were rapidly removed and frozen in optimal cutting temperature embedding compound. Sections were histochemically stained with specific markers for vascular cells and angiogenesis–related factors. The area of new retinal vessels was measured using image analysis software and compared between groups. Results: Retinal neovascularization was not significantly different between wild–type mice and MMP–9–/– mice. The MMP–2–/– mice developed significantly less extraretinal neovascularization than did wild–type mice. The mean number of extraretinal neovascular buds per cross section was significantly lower in MMP2–/– mice compared with wild–type mice (P<0.05). The expression of other angiogenesis–related factors, vascular endothelial growth factor and pigment epithelium–derived factor, was not different between wild–type mice and MMP–2 –/– mice. Conclusions: MMP–2 might be important for the regulation of retinal neovascularization. Pharmacologic intervention using MMP inhibitors might be a future therapeutic approach for angiogenic retinal diseases.

Keywords: retinal neovascularization • transgenics/knock–outs • extracellular matrix