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The roles of the Nrf2/Keap1 axis in age-related retinal degeneration

Research Project

Project/Area Number 17J10301
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Ophthalmology
Research InstitutionGifu Pharmaceutical University

Principal Investigator

齋藤 祐一  岐阜薬科大学, 薬学研究科, 特別研究員(DC1)

Project Period (FY) 2017-04-26 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2019: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2018: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2017: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsNrf2 / 酸化ストレス / オートファジー / 網膜色素上皮 / ファゴサイトーシス / p62 / Nrf2/Keap1経路 / 網膜色素上皮細胞
Outline of Annual Research Achievements

網膜色素上皮は恒常的に視細胞外節を貪食・消化することで視機能の維持に重要な役割を果たしている。この網膜色素上皮に慢性的な酸化ストレスがかかることが、難治性網膜疾患である萎縮型加齢黄斑変性症の病態形成を引き起こすと考えられているが、未だ有効な治療薬は開発されていない。そこでわれわれは酸化ストレスに応答し、生体内で多様な異物代謝関連因子を誘導する転写因子であるNF-E2-related factor 2 (Nrf2) に着目した。われわれはNrf2の活性化薬が萎縮型加齢黄斑変性症の発症に重要であると考えられる網膜色素上皮の代謝機構に及ぼす影響を検討した。
本年度は、Nrf2活性化薬RS9がAMPKα1のリン酸化を介したLC3の誘導により網膜色素上皮における視細胞外節のファゴリソソーム形成を促進することを明らかにした。さらに、マウスを用いたIn vivo死細胞ファゴサイトーシス活性評価系を確立し、RS9が光照射後の網膜色素上皮におけるファゴリソソームサイズを低下させることを明らかにした。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (20 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] A triterpenoid Nrf2 activator, RS9, promotes LC3-associated phagocytosis of photoreceptor outer segments in a p62-independent manner2020

    • Author(s)
      Saito Yuichi、Yako Tomohiro、Otsu Wataru、Nakamura Shinsuke、Inoue Yuki、Muramatsu Aomi、Nakagami Yasuhiro、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 152 Pages: 235-247

    • DOI

      10.1016/j.freeradbiomed.2020.03.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Contribution of platelet-derived growth factor signaling to retina regeneration in zebrafish2020

    • Author(s)
      Saito Yuichi、Yamaguchi Akihiro、Nakamura Shinsuke、Okuyoshi Hiroyuki、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Neuroscience Letters

      Volume: 727 Pages: 134930-134930

    • DOI

      10.1016/j.neulet.2020.134930

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of anti-osteoporosis drugs against dexamethasone-induced osteoporosis-like phenotype using a zebrafish scale-regeneration model2020

    • Author(s)
      Saito Yuichi、Nakamura Shinsuke、Chinen Naoki、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 143 Issue: 2 Pages: 117-121

    • DOI

      10.1016/j.jphs.2020.02.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Granulin 1 Promotes Retinal Regeneration in Zebrafish2018

    • Author(s)
      Tsuruma Kazuhiro、Saito Yuichi、Okuyoshi Hiroyuki、Yamaguchi Akihiro、Shimazawa Masamitsu、Goldman Daniel、Hara Hideaki
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 59 Issue: 15 Pages: 6057-6057

    • DOI

      10.1167/iovs.18-24828

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transient acceleration of autophagic degradation by pharmacological Nrf2 activation is important for retinal pigment epithelium cell survival2018

    • Author(s)
      Saito Yuichi、Kuse Yoshiki、Inoue Yuki、Nakamura Shinsuke、Hara Hideaki、Shimazawa Masamitsu
    • Journal Title

      Redox Biology

      Volume: 19 Pages: 354-363

    • DOI

      10.1016/j.redox.2018.09.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Water extract of Brazilian green propolis attenuates high glucose-induced vascular morphological abnormality in zebrafish2018

    • Author(s)
      Saito Yuichi、Gouda Takumi、Nakamura Shinsuke、Ichihara Kenji、Hara Hideaki、Shimazawa Masamitsu
    • Journal Title

      Journal of Functional Foods

      Volume: 49 Pages: 250-257

    • DOI

      10.1016/j.jff.2018.08.028

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] タウロウルソデオキシコール酸はゼブラフィッシュ網膜における桿体細胞前駆細胞の細胞周期を亢進させる2019

    • Author(s)
      齋藤 祐一、奥吉 博之、中村 信介、山口 明洋、嶋澤 雅光、永島 幹子、Peter F. Hitchcock、原 英彰
    • Organizer
      第5回ゼブラフィッシュメダカ創薬研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Tauroursodeoxycholic acid promotes cell cycle in rod progenitor cells2019

    • Author(s)
      Saito Y, Okuyoshi H, Yamaguchi A, Nakamura S, Shimazawa M, Nagashima M, Peter F. H, Hara H
    • Organizer
      Retina Workshop 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tauroursodeoxycholic acid changes retinal regeneration pattern in adult zebrafish following exposure to intense light2019

    • Author(s)
      Saito Y, Okuyoshi H, Nakamura S, Yamaguchi A, Hara H, Shimazawa M
    • Organizer
      2019 Midwest Zebrafish Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nrf2活性化薬RS9はAMPK/mTOR及びNrf2/SQSTM1シグナルの二重活性化により網膜色素上皮におけるLC3関連型ファゴサイトーシスを促進する2019

    • Author(s)
      齋藤祐一、中村信介、嶋澤雅光、原英彰
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゼブラフィッシュ鱗再生モデルを用いたステロイド性骨粗鬆症に対する水抽出プロポリスの作用評価2018

    • Author(s)
      齋藤祐一、中村信介、郷田拓実、市原賢二、嶋澤雅光、原英彰
    • Organizer
      第9回岐阜薬科大学機能性健康食品研究講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 鱗再生を利用したステロイド性骨粗鬆症薬効評価モデルの確立2018

    • Author(s)
      齋藤祐一、中村信介、郷田拓実、嶋澤雅光、原英彰
    • Organizer
      第4回ゼブラフィッシュメダカ創薬研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 視細胞外節のLC3関連型ファゴサイトーシスに対するNrf2活性化薬の影響2018

    • Author(s)
      齋藤祐一、中村信介、嶋澤雅光、原英彰
    • Organizer
      第11回オートファジー研究会 若手の会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 網膜色素上皮の視細胞外節ファゴサイトーシスにおけるNrf2の関与2018

    • Author(s)
      齋藤祐一、中村信介、嶋澤雅光、原英彰
    • Organizer
      第38回日本眼薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゼブラフィッシュ網膜再生における血小板由来成長因子 (PDGF) の関与2018

    • Author(s)
      山口明洋、齋藤祐一、奥吉博之、中村信介、嶋澤雅光、原英彰
    • Organizer
      第38回日本眼薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A novel Nrf2 activator RS9 promotes phagocytosis in retinal pigment ephithelium2018

    • Author(s)
      Saito Y., Inoue Y., Nakamura S., Shimazawa M., Hara H.
    • Organizer
      the 2nd International Conference & Expo on Pharmacology & Regulatory Affairs
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel Nrf2 activator RS9 protects ARPE-19 cells from oxidative stress induced by NaIO3 via autophagic pathway2018

    • Author(s)
      Saito Y., Nakamura S., Shimazawa M., Hara H.
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel Nrf2 activator RS9 protects ARPE-19 cells from oxidative stress induced by NaIO3 via autophagic pathway2018

    • Author(s)
      Yuichi Saito, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
    • Organizer
      the 18th World Congress of Basic and Clinical Pharmacology (WCP2018)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel Nrf2 activator RS9 promotes phagocytosis in retinal pigment ephithelium2018

    • Author(s)
      Yuichi Saito, Yuki Inoue, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
    • Organizer
      the 2nd International Conference & Expo on Pharmacology & Regulatory Affairs
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト網膜色素上皮細胞を用いたヨウ素酸ナトリウム誘発障害に対する Nrf2活性化薬の保護作用2017

    • Author(s)
      齋藤祐一、井上雄有輝、嶋澤雅光、原英彰
    • Organizer
      第37回日本眼薬理学会
    • Related Report
      2017 Annual Research Report

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Published: 2017-05-25   Modified: 2024-03-26  

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