| Project/Area Number |
12671698
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OHNO Kyoko Tokyo Medical and Dental University, Gruduate School, Assistant Professor, 大学院・医歯学総合研究科, 講師 (30262174)
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIZUKI Manabu Tokyo Medical and Dental University, Gruduate School, Chairman and Professor, 大学院・医歯学総合研究科, 教授 (10010464)
田中 住美 東京医科歯科大学, 医学部・附属病院, 講師
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Ocular angiogenesis / matrix metallopisteinese / retinal neovascularization / choroidal neovascularization / knockout mouse / 網膜血管新生 / 脈絡膜血管新生 / マトリックス メタロプロテアーゼ / 血管新生 / matrix metalloproteinase / 基底膜分解 |
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| Research Abstract |
Purpose : To study the putative role of endogenous MMPs in ocular neovascularizarion, we used an established mouse model and compared the retinal and choroidal neovascularizarion observed in wild-type mice to that found in mice lacking MMP-2 or MMP-9 gene.
Methods : C57BI/6 (MMP2+/+, MMP9+/+), MMP-2-deficinet (MMP2-/-) and MMP-9-deficient (MMP9-/-) mice were used in the experiments. Oxygen-induced retinopathy and laser-induced choroidal neovascularization (CNV) were indeced in these mice. Their eyes were rapidly removed and frozen in optimal cutting temperature embedding compound and sections were histochemically stained with specific marker for vascular cells. The area of retinal of choroidal new vessels was measured by computer with image analysis sofuware and compared between groups statistically.
Results : The MMP2 -/- mice and MMP9 -/- mice developed sinificantly less extensive extraretinal neovascularization than the wild-type mice did. The mean number of extraretinal neovascular buds per cross section was significantly higher in wild-type mice compared with MMP2 -/- mice eyes (P<0.05) and MMP9 -/- mice eyes (P<0.05). On the other hand, measurement of CNV lesion size by image analysis demonstrated that there was no significant differrence in the integrated area of lectin staining per CNV lesion in MMP-knockout mice compared with wild type mice.
Conclusions : This study has first clarified that MMP-2 and MMP-9 may be of particular importance in the regulation of retinal neovascularization, using gene-deficiency mice models. Phamacological intervention using MMP inhibitors may become an alternative thrapeutic approach to angiogenic retinal diseases in the future.
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