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Investigation of novel drugs for inducing retinal regeneration

Research Project

Project/Area Number 19K09936
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Hara Hideaki  岐阜薬科大学, 薬学部, 学長 (20381717)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords網膜再生 / ゼブラフィッシュ / PDGF / TUDCA / 血小板由来成長因子 / 再生医学 / 薬理学
Outline of Research at the Start

視覚を維持するために必要な網膜の細胞は一度変性してしまうとほとんど取り戻すことができない。薬物を用いて変性後の網膜を再生させる方法が確立できれば難治性の網膜変性疾患における中途失明を大幅に減らすことが可能な新たな治療戦略となる。そこで、本研究ではまず高い再生能をもつゼブラフィッシュを用いていくつかの再生関連因子を誘導する網膜再生候補化合物のスクリーニングを行う。その後、再生誘導作用の機序別に分類した各種薬物を組み合わせることにより考案した再生誘導法を哺乳類であるマウスに適用し、臨床応用可能な強い網膜再生誘導作用を有する薬剤性再生誘導法の確立を目指す。

Outline of Final Research Achievements

We investigated new retinal regeneration inducers using zebrafish, which causes physiological retinal regeneration in adults. In this study, we identified PDGF and TUDCA as novel factors / drugs with retinal regeneration promoting activity. In addition, the analysis of PDGF function suggested that each growth factors have different functions in the regeneration process and act in a complex manner. Though TUDCA alone does not induce Muller glia activation, it has been shown that it may be used as a pharmacological method for inducing retinal regeneration in combination with Muller glia activating factors including growth factors.

Academic Significance and Societal Importance of the Research Achievements

本研究においては、網膜再生促進作用を有する新規因子・薬物としてPDGF及びTUDCAを見出し、それらの作用機序の一端を明らかにした。これらの発見は学術的な新規性を有しているのみならず、未だ達成されていない哺乳類の網膜再生制御を行うための重要な知見であり、本研究の成果は網膜再生研究の発展に貢献するものである。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2020

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Tauroursodeoxycholic Acid Promotes Neuronal Survival and Proliferation of Tissue Resident Stem and Progenitor Cells in Retina of Adult Zebrafish2020

    • Author(s)
      Saito Yuichi、Okuyoshi Hiroyuki、Nakamura Shinsuke、Otsu Wataru、Yamaguchi Akihiro、Hitchcock Peter F.、Nagashima Mikiko、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      BPB Reports

      Volume: 3 Issue: 3 Pages: 92-96

    • DOI

      10.1248/bpbreports.3.3_92

    • NAID

      130007944888

    • ISSN
      2434-432X
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Therapeutic Effects of Iron Chelation in Atorvastatin-Induced Intracranial Hemorrhage of Zebrafish Larvae2020

    • Author(s)
      Nakamura Shinsuke、Saito Yuichi、Gouda Takumi、Imai Takahiko、Shimazawa Masamitsu、Nishimura Yuhei、Hara Hideaki
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 29 Issue: 11 Pages: 105215-105215

    • DOI

      10.1016/j.jstrokecerebrovasdis.2020.105215

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 網膜オルガノイドを用いた糖尿病網膜症モデルの開発2022

    • Author(s)
      中村信介、稲垣賢、青山八曇、青島弘汰、大津航、舩戸道徳、嶋澤雅光、高橋一浩、原英彰
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトiPS細胞由来血管構造を有する網膜オルガノイドの作製2021

    • Author(s)
      稲垣賢、青山八曇、舩戸道徳、中村信介、嶋澤雅光、金子英雄、原英彰
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Triterpenoid Nrf2 activator, RS9, promotes LC3-associated phagocytosis of photoreceptor outer segments without p62 induction.2020

    • Author(s)
      Nakamura S, Saito Y, Yako T, Otsu W, Inoue Y, Muramatsu A, Nakagami Y, Shimazawa M and Hara H
    • Organizer
      ARVO 2020 Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] アトルバスタチン誘発ゼブラフィッシュ脳内出血モデルの作製と鉄キレート剤の効果2020

    • Author(s)
      中村 信介、齋藤 祐一、今井 貴彦、郷田 拓実、嶋澤 雅光、西村 有平、原 英彰
    • Organizer
      第63回日本脳循環代謝学会学術集会
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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