Matrix metalloproteinase–2 is not essential for either physiologic or pathologic retinal angiogenesis in the mouse

Abstract

Abstract: : Purpose:Earlier studies have suggested a role for metalloproteinase–2 (MMP–2) in angiogenesis, including retinal neovascularization. To investigate this further, we have studied physiologic retinal vascularization and pathologic ischemia–induced retinal neovascularization in MMP–2–deficient and wild–type mice. Methods: Normal vascular development of the retina was studied in retinal flatmounts from MMP–2 deficient and wild–type mice whereas pathologic retinal neovascularization was analyzed in a murine model of ischemia–induced retinopathy. The time–course of MMP–2 mRNA expression was determined by in situ hybridization using anti–sense and sense cRNA probes. Results: The formation of radially growing and branching vessels representing the formation of a retinal vascular plexus was detected in both MMP–2 deficient and wild–type mice. The outgrowth of the vascular plexus was however more rapid in the MMP–2 deficient mice as compared to the wild–type mice (p<0.05). There was no apparent correlation between formation of the vascular plexus and expression of MMP–2 mRNA. In ischemia–induced retinopathy there was an increased formation of extraretinal neovascular tufts in the MMP–2– deficient mice as compared to the wild–type mice (p<0.01). The formation of neovascular tufts was not correlated with any detectable expression of MMP–2 mRNA. Conclusions: The inverse correlation between the presence of MMP–2 and the growth of the retinal vascular plexus or the formation of neovascular extraretinal tufts shows that MMP–2 is not essential for either physiologic retinal vascularization or pathologic retinal neovascularization. A dual role of MMP–2 in retinal neovascularization should be considered when discussing MMP inhibition as a possible treatment for neovascular retinopathies.

Keywords: extracellular matrix • hypoxia • retinopathy of prematurity