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The molecular and functional analysis of retinal microglia in diabetic retinopathy

Research Project

Project/Area Number 17K16984
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionJuntendo University

Principal Investigator

Usui-Ouchi Ayumi  順天堂大学, 医学部, 非常勤助教 (80645664)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsマイクログリア / 糖尿病網膜症 / 網膜血管新生 / 未熟児網膜症 / 加齢黄斑変性症 / 網膜マイクログリア / 網膜新生血管
Outline of Final Research Achievements

We investigated that the interaction between the pathology of neovascular formation, which is the cause of severe visual function loss in diabetic retinopathy and the mechanism of microglial activation in retina. In a mouse model of ischemic retinopathy, we have revealed that Tgfβ signal in retinal microglia regulates microglia activation and plays an essential role in neovascular tufts formation in the retina. Moreover, it was also suggested that retinal microglia were critical for retinal neovascular formation in Vldlr knock-out mice, and the pharmacological modulation of microglia rescued the neovascular tufts formation and improved visual function loss.

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜症は、近年、硝子体手術機器や抗VEGF 薬など薬物療法の進歩により、治療成績は向上してきているものの、発症や進行を予防する治療法は存在せず、我が国の中途失明原因の第3位であり、年間約3000人が失明に近い状態に至っている。本研究成果は、網膜マイクログリアが、網膜病的血管新生を制御する可能性を示しており、糖尿病網膜症を始め重篤な視機能障害をもたらす未熟児網膜症や加齢黄斑変性症など、病的血管新生を主病態とする疾患において、従来の抗VEGF療法のみならず、マイクログリアをターゲットとした治療の有効性を示唆する重要な知見である。

Report

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

    (14 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] The Scripps Research Institute(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The Scripps Research Institute(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Scripps research institute(U.S.A.)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Retinal microglia are critical for subretinal neovascular formation2020

    • Author(s)
      Usui-Ouchi Ayumi、Usui Yoshihiko、 Kurihara Toshihide、 Aguilar Edith、Dorrell Michael、Ideguchi Yoichiro、Sakimoto Susumu、Bravo Stephen、and Friedlander Martin
    • Journal Title

      JCI insight

      Volume: in press

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-VEGF therapy: higher potency and long-lasting antagonism are not necessarily better2019

    • Author(s)
      Usui-Ouchi Ayumi、Friedlander Martin
    • Journal Title

      Journal of Clinical Investigation

      Volume: 129 Issue: 8 Pages: 3032-3034

    • DOI

      10.1172/jci129862

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three Cases of Creutzfeldt-Jakob Disease with Visual Disturbances as Initial Manifestation2019

    • Author(s)
      Sakuma Toshiro、Watanabe Satoshi、Ouchi Ayumi、Sakanishi Yoshihito、Mizota Atsushi、Ebihara Nobuyuki
    • Journal Title

      Case Reports in Ophthalmology

      Volume: 10 Issue: 3 Pages: 349-356

    • DOI

      10.1159/000503274

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 飛蚊症の自覚から網膜剥離発見までの期間について2019

    • Author(s)
      佐久間 俊郎, 大内 亜由美, 坂西 良仁, 伊藤 玲, 清川 正敏, 海老原 伸行
    • Journal Title

      眼科臨床紀要

      Volume: 12 (1) Pages: 5-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特集 第71回日本臨床眼科学会講演集[6] 原著 治療開始後に肺結核への罹患が判明した糖尿病網膜症3例2018

    • Author(s)
      玉城麻夏、大内亜由美、坂西良仁、李亜美、海老原伸行
    • Journal Title

      臨床眼科

      Volume: 72 Issue: 8 Pages: 1161-1167

    • DOI

      10.11477/mf.1410212793

    • ISSN
      0370-5579, 1882-1308
    • Year and Date
      2018-08-15
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 基礎研究コラム 15.microRNAの臨床応用の可能性2018

    • Author(s)
      大内亜由美
    • Journal Title

      あたらしい眼科

      Volume: 35(8) Pages: 1099-1099

    • Related Report
      2018 Research-status Report
  • [Journal Article] The peroxisome proliferator-activated receptor pan-agonist bezafibrate suppresses microvascular inflammatory responses of retinal endothelial cells and vascular endothelial growth factor production in retinal pigmented epithelial cells.2017

    • Author(s)
      Usui-Ouchi A, Ouchi Y, Ebihara N.
    • Journal Title

      Int Immunopharmacol.

      Volume: 52 Pages: 70-76

    • DOI

      10.1016/j.intimp.2017.08.027

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells: Focus on Mast Cell Tryptase.2017

    • Author(s)
      Arai R, Usui-Ouchi A, Ito Y, Mashimo K, Murakami A, Ebihara N.
    • Journal Title

      Mediators Inflamm.

      Volume: 29 Pages: 3124753-3124753

    • DOI

      10.1155/2017/3124753

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-term outcomes in patients with branch retinal vein occlusion who received intravitreal aflibercept with or without intravitreal ranibizumab.2017

    • Author(s)
      Sakanishi Y, Usui-Ouchi A, Tamaki K, Mashimo K, Ito R, Ebihara N.
    • Journal Title

      Clin Ophthalmol.

      Volume: 3 Pages: 829-834

    • DOI

      10.2147/opth.s133594

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The role of Acid-sensing ion channel 1a in a mouse model of ischemic retinopathy2019

    • Author(s)
      Ayumi Ouchi, Edith Aguilar, Kyle Marra, Min Qiang, Yang Guang, Richard Lerner, Martin Friedlander
    • Organizer
      ARVO annual meeting 2019
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Extracellular vesicles shed from endothelial colony forming seeks (ECFCs) with high expression of CD44 are paracrine mediators of neurovasculotrophic retinal repair.2019

    • Author(s)
      Kyle Marra, Edith Aguilar, Ayumi Ouchi, Susumu Sakimoto, Martin Friedlander
    • Organizer
      ARVO annual meeting 2019
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Int'l Joint Research

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

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