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Role of complement factor MASP-1/3 in age-related macular degeneration and therapeutic effect of novel complement inhibitors

Research Project

Project/Area Number 17K16975
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionFukushima Medical University

Principal Investigator

Omori Tomoko  福島県立医科大学, 医学部, 助教 (50754222)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords加齢黄斑変性 / 補体 / 免疫学
Outline of Final Research Achievements

We aimed to clarify the role of complement factor MASP-1/3 of the lectin and alternative pathways in the development of neovascular age-related macular degeneration (nAMD). In patients with nAMD, the ratios of aqueous humor levels of C4a/C4 and C3a/C3 were significantly higher than in cataract patients, providing conclusive evidence for intraocular activation of the lectin and/or classical pathway in nAMD eyes. Furthermore, using mouse model of laser-induced choroidal neovascularization, which has been used extensively studies of nAMD, we found that the nAMD-like lesion was alleviated in mice deficient for MASP-1/3 compared to wild-type mice, although there was no significant difference between them. Our results strongly suggest the contribution of MASP-1/3 in the development of nAMD.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、第二経路に加え、眼内におけるレクチン経路と古典経路の一方または両方の活性化が滲出型加齢黄斑変性の病態に関与することが明らかとなった。よって、MASP-1/3を標的とする治療法が有効である可能性が強く示唆された。これらの成果は、滲出型加齢黄斑変性の病態における補体の関与への理解を深め、滲出型加齢黄斑変性の新規治療法や新規診断法の開発に繋がると期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report

Research Products

(10 results)

All 2020 2019 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Evidence for Activation of Lectin and Classical Pathway Complement Components in Aqueous Humor of Neovascular Age-Related Macular Degeneration.2020

    • Author(s)
      Omori T, Oguchi Y, Machida T, Kato Y, Ishida Y, Ojima A, Itagaki K, Shintake H, Tomita R, Kasai A, Sugano
    • Journal Title

      Ophthalmic Research

      Volume: 63 Pages: 252-258

    • DOI

      10.1159/000503258

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel complement inhibitor sMAP-FH targeting both the lectin and alternative complement pathways2020

    • Author(s)
      Takasumi M, Omori T, Machida T, Ishida Y, Hayashi M, Suzuki T, Homma Y, Endo Y, Takahashi M, Ohira H, Fujita T, Sekine H
    • Journal Title

      The FASEB Journal

      Volume: 34 Pages: 6598-6612

    • DOI

      10.1096/fj.201902475r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anaphylatoxin Concentration in Aqueous and Vitreous Humor in the Eyes With Vitreoretinal Interface Abnormalities2020

    • Author(s)
      Yasuharu Oguchi , Tetsuju Sekiryu , Tomoko Omori , Yutaka Kato , Masashi Ogasawara , Yukinori Sugano , Kanako Itagaki , Akira Ojima , Takeshi Machida , Hideharu Sekine
    • Journal Title

      Experimental Eye Research

      Volume: 195 Pages: 108025-108025

    • DOI

      10.1016/j.exer.2020.108025

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cutting Edge: Role of MASP-3 in the physiological activation of factor D of the alternative complement pathway2019

    • Author(s)
      Manabu Hayashi, Takeshi Machida, Yumi Ishida, Yusuke Ogata, Tomoko Omori, Mika Takasumi, Yuichi Endo, Toshiyuki Suzuki, Masayuki Sekimata, Yoshimi Homma, Masahito Ikawa, Hiromasa Ohira, Teizo Fujita, and Hideharu Sekine
    • Journal Title

      the J Immunol

      Volume: 203 Pages: 1411-1416

    • DOI

      10.4049/jimmunol.1900605

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Complement activation product levels in aqueous humor of patients with age-related macular degeneration2019

    • Author(s)
      Kato Y, Sekiryu T, Oguchi Y, Omori T, Machida T, Sekine H
    • Organizer
      ARVO annual meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 加齢黄斑変性におけるレクチン経路の関与の可能性2019

    • Author(s)
      大森智子,大口泰治, 町田豪, 石田由美, 加藤寛, 石龍鉄樹, 関根英治
    • Organizer
      第56回日本補体学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MASP-1、MASP-3はレクチン経路、第二経路の活性化に独立して寄与する2018

    • Author(s)
      林学、石田由美、町田豪、尾形裕介、大森智子、高住美香、遠藤雄一、関亦正幸、伊川正人、大平弘正、藤田禎三、関根英治
    • Organizer
      第55回日本補体学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 滲出型加齢黄斑変成の前房水中補体分解産物の検討2018

    • Author(s)
      加藤寛、大口泰治、大森智子、町田豪、関根英治、石龍鉄樹
    • Organizer
      第38回日本眼薬理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] MASP-1 and MASP-3 play independent roles in activation of the lectin and alternative complement pathways2018

    • Author(s)
      Manabu Hayashi, Yumi Ishida, Takeshi Machida, Yusuke Ogata, Tomoko Omori, Mika Takasumi, Yuishi Endo, Masahiko Ikawa, Hiromasa Ohira, Teizo Fujita, Hideharu Sekine
    • Organizer
      XXVII International Complement Workshop
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 補体レクチン経路と第二経路を標的とする新規抗補体薬sMAP-fHの開発2017

    • Author(s)
      高住美香、高橋実、大森智子、町田豪、石田由美、関根英治
    • Organizer
      第54回日本補体学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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