Reduced Retinal Angiogenesis in MMP-2–Deficient Mice
doi: 10.1167/iovs.03-0249
pmid: 14638740
Reduced Retinal Angiogenesis in MMP-2–Deficient Mice
To study the putative role of endogenous matrix metalloproteinases (MMPs) in retinal neovascularization, an established mouse model was used to compare the retinal neovascularization observed in wild-type mice with that in mice without the MMP-2 or -9 genes.C57Bl/6 (MMP-2(+/+) and -9(+/+)), MMP-2-deficient (MMP-2(-/-)), 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.Retinal neovascularization was not significantly different between wild-type and MMP-9(-/-) mice. The MMP-2(-/-) mice had significantly less extraretinal neovascularization than did wild-type mice. The mean number of extraretinal neovascular buds per cross section was significantly lower in MMP-2(-/-) mice than in 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 and MMP-2(-/-) mice.MMP-2 may be essential in the regulation of retinal neovascularization. Pharmacologic intervention using MMP inhibitors may be a future therapeutic approach for angiogenic retinal diseases.
Mice, Knockout, Vascular Endothelial Growth Factor A, Infant, Newborn, Proteins, Dextrans, Retinal Neovascularization, Immunohistochemistry, Mice, Inbred C57BL, Disease Models, Animal, Mice, Animals, Newborn, Matrix Metalloproteinase 9, Animals, Humans, Matrix Metalloproteinase 2, Retinopathy of Prematurity, Nerve Growth Factors, Eye Proteins, Fluorescein-5-isothiocyanate, Serpins
Mice, Knockout, Vascular Endothelial Growth Factor A, Infant, Newborn, Proteins, Dextrans, Retinal Neovascularization, Immunohistochemistry, Mice, Inbred C57BL, Disease Models, Animal, Mice, Animals, Newborn, Matrix Metalloproteinase 9, Animals, Humans, Matrix Metalloproteinase 2, Retinopathy of Prematurity, Nerve Growth Factors, Eye Proteins, Fluorescein-5-isothiocyanate, Serpins
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