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Glial activation induced by unsaturated aldehyde acrolein in diabetic retinopathy

Research Project

Project/Area Number 18K09393
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionHokkaido University

Principal Investigator

Noda Kousuke  北海道大学, 医学研究院, 准教授 (90296666)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords網膜グリア細胞 / 不飽和アルデヒド / 糖尿病網膜症
Outline of Final Research Achievements

Diabetic retinopathy (DR) is a retinal microvascular complication of diabetes and is still a leading cause of visual impairment in the developed countries. Previous studies revealed that retinal glial cell migration is involved in the fibrovascular tissue formation, leading to the severe complications in patients with DR; however, the detailed mechanisms remains unclear.
Acrolein is a highly reactive unsaturated aldehyde that causes dysfunction of multiple proteins. In this study, we explored the regulatory mechanisms responsible for retinal glial cell migration induced by unsaturated aldehyde acrolein and found that i) acrolein exerted potent cellular toxicity at a high concentration; however, sublethal concentration of acrolein slightly induces viability and migratory property of retinal glial cells; and ii) inflammatory chemokine CXCL1 is a mediator of glial cell migration induced by acrolein.

Academic Significance and Societal Importance of the Research Achievements

近年、糖尿病網膜症の病態は少しずつ明らかとされ、同疾患に関する理解の蓄積、そしてその結果として糖尿病黄斑浮腫治療に臨床導入されたVEGF阻害剤の開発は糖尿病網膜症の治療体系を大きく変えた。しかしその一方で、糖尿病網膜症の病態、特に線維血管組織の形成メカニズムには不明な点が未だ多く存在する。本研究は、線維血管組織の形成に重要な役割を演じると考えられている網膜グリア細胞の遊走メカニズムについて検討を行い、その一部を明らかとした。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report

Research Products

(21 results)

All 2020 2019 2018

All Journal Article (10 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Pathological Role of Unsaturated Aldehyde Acrolein in Diabetic Retinopathy2020

    • Author(s)
      Murata Miyuki、Noda Kousuke、Ishida Susumu
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 589531-589531

    • DOI

      10.3389/fimmu.2020.589531

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diabetic Cataract in Spontaneously Diabetic Torii Fatty Rats2020

    • Author(s)
      Kikuchi Kasumi、Murata Miyuki、Noda Kousuke、Kase Satoru、Tagawa Yoshiaki、Kageyama Yasushi、Shinohara Masami、Sasase Tomohiko、Ishida Susumu
    • Journal Title

      Journal of Diabetes Research

      Volume: 2020 Pages: 3058547-3058547

    • DOI

      10.1155/2020/3058547

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice2020

    • Author(s)
      Liu Ye、Noda Kousuke、Murata Miyuki、Wu Di、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Pages: 2242-2242

    • DOI

      10.3390/jcm9072242

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 次世代の抗VEGF製剤2020

    • Author(s)
      野田航介
    • Journal Title

      あたらしい眼科

      Volume: 37 Pages: 261-266

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 治療薬解説 眼科における抗VEGF療法2020

    • Author(s)
      野田航介
    • Journal Title

      カレントテラピー

      Volume: 38 Pages: 175-179

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 糖尿病網膜症の薬物治療に関する近年の動向2020

    • Author(s)
      野田航介
    • Journal Title

      糖尿病合併症

      Volume: 34 Pages: 23-26

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Unsaturated Aldehyde Acrolein Promotes Retinal Glial Cell Migration2019

    • Author(s)
      Murata Miyuki、Noda Kousuke、Yoshida Shiho、Saito Michiyuki、Fujiya Akio、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 60 Pages: 4425-4435

    • DOI

      10.1167/iovs.19-27346

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells2018

    • Author(s)
      Yoshida Shiho、Murata Miyuki、Noda Kousuke、Matsuda Takashi、Saito Michiyuki、Saito Wataru、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 62 Issue: 2 Pages: 256-264

    • DOI

      10.1007/s10384-017-0555-4

    • ISSN
      0021-5155, 1613-2246
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] VEGF阻害薬と次の分子標的. シンポジウム2:硝子体内注射の現況と進展2018

    • Author(s)
      野田航介
    • Journal Title

      眼薬理

      Volume: 32 Pages: 51-54

    • Related Report
      2018 Research-status Report
  • [Journal Article] 第121回 日本眼科学会総会 評議員会指名講演Ⅲ 眼科のトランスレーショナルリサーチ 多機能蛋白質に着目した糖尿病網膜症に対する創薬研究2018

    • Author(s)
      野田航介
    • Journal Title

      日眼会誌

      Volume: 122

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 増殖糖尿病網膜症患者の硝子体中アクロレイン結合蛋白と単球走化性因子2020

    • Author(s)
      村田美幸、福津佳苗、野田航介、吉田志帆、神田敦宏、石田 晋
    • Organizer
      第26回日本糖尿病眼学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] SDT fatty ラット水晶体におけるポリオール経路と酸化ストレスの継時的解析2020

    • Author(s)
      菊地香澄、村田美幸、野田航介、神田敦宏、加瀬 諭、影山 靖、篠原雅巳、笹瀬智彦、石田 晋
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アクロレインによる網膜ミュラーグリア細胞の遊走作用とROCK1の関与2020

    • Author(s)
      福津佳苗、村田美幸、野田航介、吉田志帆、神田敦宏、石田 晋
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Diabetic Cataract in Spontaneously Diabetic Torii Fatty Rats2019

    • Author(s)
      Kikuchi K, Noda K, Murata M, Tagawa Y, Kanda A, Kase S, Kageyama Y, Shinohara M, Sasase T, Ishida S
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hypoxia inducible factor-1 regulates spermine oxidase leading to acrolein generation in Muller Glial cells2019

    • Author(s)
      Wu D, Noda K, Murata M, Liu Y, Kanda A and Ishida S
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spontaneously Diabetic Torii fatty ラット網膜における炎症性サイトカインの発現解析2019

    • Author(s)
      菊地香澄、野田航介、村田美幸、神田敦宏、加瀬 諭、影山 靖、篠原雅巳、笹瀬智彦、石田 晋
    • Organizer
      第25回日本糖尿病眼学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Spontaneously Diabetic Torii fatty ラットにおける糖尿病白内障の検討2019

    • Author(s)
      菊地香澄、野田航介、村田美幸、田川義晃、神田敦宏、加瀬 諭、影山 靖、篠原雅巳、笹瀬智彦、石田 晋
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Hypoxia aggravates acrolein generation via HIF-1/SMOX pathway in glial cells2019

    • Author(s)
      Wu D, Murata M, Noda K, Liu Y, Kanda A, Ishida S
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 糖尿病黄斑浮腫に対する抗VEGF療法とbeyond VEGF. シンポジウム「糖尿病網膜症治療の近未来」2018

    • Author(s)
      野田航介
    • Organizer
      第24回糖尿病眼学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 網膜硝子体疾患と炎症2018

    • Author(s)
      野田航介
    • Organizer
      第75回日本眼科医会生涯教育講座
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 糖尿病網膜症病態におけるvascular adhesion protein-1の役割. シンポジウム「糖尿病網膜症:臨床応用を目指した基礎研究による新たな病態理解」2018

    • Author(s)
      野田航介
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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