Reduced retinal angiogenesis in MMP-2-deficient mice.

Abstract

PURPOSE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Kyoko Ohno-Matsui, Tomoko Uetama, Takeshi Yoshida, Masato Hayano, Takeshi Itoh, Ikuo Morita, Manabu Mochizuki
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 44 Issue 12 Pg. 5370-5 (Dec 2003) ISSN: 0146-0404 [Print] United States
• PMID: 14638740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dextrans
• Eye Proteins
• Nerve Growth Factors
• Proteins
• Serpins
• Vascular Endothelial Growth Factor A
• fluorescein isothiocyanate dextran
• pigment epithelium-derived factor
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Fluorescein-5-isothiocyanate

Topics

• Animals
• Animals, Newborn
• Dextrans
• Disease Models, Animal
• Eye Proteins
• Fluorescein-5-isothiocyanate (analogs & derivatives)
• Humans
• Immunohistochemistry
• Infant, Newborn
• Matrix Metalloproteinase 2 (deficiency, physiology)
• Matrix Metalloproteinase 9 (deficiency, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nerve Growth Factors
• Proteins (metabolism)
• Retinal Neovascularization (enzymology, etiology, pathology, prevention & control)
• Retinopathy of Prematurity (complications)
• Serpins (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)