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The role of matrix metallopisteinese in ocular argiogenesis

Research Project

Project/Area Number 12671698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionTokyo Medical and Dental University

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)

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
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsOcular 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
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.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] K.Ohno-Matsui, et al.: "Novel mechanism for age-related macular degeneration : an equilibrium shift between the angiogenesis factors VEGF and PEDF"J Cell Physiol. 189. 323-333 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Ohno-Matsui, et al.: "Inducible expression of VEGF in adult mice causes severe proliferative retinopathy and retinal detachment"Am J Pathol. 160. (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yoshida, et al.: "Long-term visual prognosis of choroidal neovascularization in high myopia, A comparison between age groups"Ophthalmology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Baba, et al.: "Optical coherence topography of choroidal neovascularization in high myopia"Acta Ophthalmol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Takei, et al.: "Indocyanine green angiographic findings of acute retinal necrosis"Jpn J Ophthalmol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Ohno-Matsui, et al.: "Spontaneous involution of a large retinal arterial macroaneurysm"Acta Ophthalmol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 大野 京子 他: "血管新生研究の新展開"医業ジャーナル社. 391 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno-Matsui K, Hirose A, Yamamoto S, Saikia J, Okamoto N, Chang M, Bok D, Zack DJ, Campochiaro PA.: "Inducible expression of VEGF in adult mice causes severe proliferative retinopathy and retinal detachment"Am J Pathol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno-Matsui K, Morita I, Tombran-Tink J, Mrazek D, ' UetamaT, Hayano M, MurotaS, Mochizuki M.: "Novel mechanism for age-related macular degeneratioin : An equilibrium shift between the angiogenesis factors VEGF and PEDF"J Cell Physiol. 189. 323-333 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshida T, Ohno-Matsui K, Ohtake Y, TakashimaT, Futagami S, Baba T, Yasuzumi K, Tokoro T, Mochizuki M.: "Long-term visual prognosis of choroidal neovascularizarion in high myopia. A comparison between age groups"Ophthalmology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Baba T, Ohno-Matsui K, YoshidaT, Yasuzumi K, Futagami S, Tokoro T, Mochizuki M.: "Optical coherence tomography of choroidal neovascularization in high myopia"Acta Ophthalmol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takei H, Ohno-Matsui K, Hayano M, Mochizuki M: "Indocyanine green angiographic findings of acute retinal necrosis"Jpn J. Ophthal.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takashima T, Yokoyana T, Futagami S, Ohno-Matsui K, Tanaka H, Tokoro T, Mochizuki M.: "The quality of life in patients with pathologic myopia"Jpn J Ophthalmol.. 45. 84-92 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] NakayamaT, Toyoda H, Ohno K, Yoshiike N, Futagami T.: "Validity, reliability and acceptability of the Japanese version of the general well-being schedule (GWBS)"Quality of Life Research. 9. 529-539 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujita H, Ohno-Matsui K, Futagami S, Tokoro T: "Case report. Indocyanine green dye leakage from retinal artery in branch retinal vein occlusion"Jpn J Ophthalmol.. 44. 277-282 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno-Matsui K, Hayano M, Futagami S,TokoroT, Ohno S: "Spontaneous involution of a large retinal arterial macroaneurysm"Acta Ophthalmol.. 78. 114-117 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohno-Matsui K.: "Novel mechanism for age-related macular degeneration : An equilibrium shift between the angiogenesis factors VEGF and PEDF"J Cell Physiol. 189(3). 323-333 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohno-Matsui K.: "Inducible expression of VEGF in adult mice causes severe proliferative retinopathy and retinal detachment"Am J Pathol. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida T.: "Long-term cisual prognosis of choroidrl reovasaulamzation in high umyoeis A companison leetireen age grayis"Ophthalmology. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Baba T.: "optical coherence tomography of choroidrl reovasaulamzation in high umyoeis A companison leetireen age grayis"Acta Oplthelmol. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Takayuki Takashima: "The quality of life in patients with pathologic myopia."Japanese Journal of Ophthalmology. 45(1). 84-92 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeo Nakayama: "Validity, reliability and acceptability of the Japanese version of the General well-being schedule (GWBS)."Quality of Life Research. 9. 529-539 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大野京子: "血管新生研究の新展開"医薬ジャーナル社. 391 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大野京子: "眼科診療プラクティス変性近視"文光堂. 136 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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