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Development of treatment for Bietti crystalline dystrophy

Research Project

Project/Area Number 17K16967
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionKyoto University

Principal Investigator

Hata Masayuki  京都大学, 医学研究科, 助教 (70748269)

Research Collaborator IKEDA Hanako  京都大学, 医学部附属病院 臨床研究総合センター, 准教授
ARITA Makoto  理化学研究所, 統合生命医科学研究センター, チームリーダー
IWAI Sachiko  京都大学, 眼科, 特定研究員
KAWAGUCHI Eri  京都大学, 眼科, 実験補佐員
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsクリスタリン網膜症 / 網膜変性疾患 / 疾患特異的iPS細胞 / 網羅的脂質解析 / 遊離コレステロール / シクロデキストリン誘導体 / CYP4V2 / iPS細胞 / 脂質代謝 / 創薬
Outline of Final Research Achievements

In this study, we generated human RPE cells from induced pluripotent stem cells (iPSCs) derived from BCD patients carrying a CYP4V2 mutation. We successfully established BCD patient-specific iPSC-RPE cells, an in vitro model of BCD. BCD iPSC-RPE cells showed degenerative changes of vacuolated cytoplasm. BCD iPSC-RPE cells exhibited lysosomal dysfunction and impairment of autophagy flux, followed by cell death. Lipidomic analyses revealed the glucosylceramide and free cholesterol accumulation in BCD-affected cells. We found that reducing free cholesterol by cyclodextrins or δ-tocopherol in RPE cells rescued BCD phenotypes.

Academic Significance and Societal Importance of the Research Achievements

現時点で治療法のないクリスタリン網膜症の病態の理解よび治療法の開発に繋がる研究であり、その意義は非常に大きいと考える。本研究で有効性が明らかとなったシクロデキストリン誘導体は、同じく難病であるニーマンピック病C型の中枢神経症状に効果が期待されている化合物であり、臨床応用に向けて既に開発がすすめられている。我々は、眼疾患に対する投与方法の検討などを行い、クリスタリン網膜症に対しても臨床応用を進めていきたい。

Report

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

    (7 results)

All 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Reduction of lipid accumulation rescues Bietti’s crystalline dystrophy phenotypes2018

    • Author(s)
      Hata Masayuki、Ikeda Hanako O.、Iwai Sachiko、Iida Yuto、Gotoh Norimoto、Asaka Isao、Ikeda Kazutaka、Isobe Yosuke、Hori Aya、Nakagawa Saori、Yamato Susumu、Arita Makoto、Yoshimura Nagahisa、Tsujikawa Akitaka
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 15 Pages: 3936-3941

    • DOI

      10.1073/pnas.1717338115

    • NAID

      120006416205

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Pathologic clarification and novel therapies development of Bietti crystalline dystrophy.2018

    • Author(s)
      Hata M
    • Organizer
      EURETINA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathologic clarification and novel therapies development of Bietti crystalline dystrophy2017

    • Author(s)
      Masayuki Hata
    • Organizer
      Senju ARVO meeting 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] クリスタリン網膜症の病態解明と新規治療法の開発2017

    • Author(s)
      畑 匡侑、池田 華子、有田 誠 、辻川 明孝
    • Organizer
      7th Wakamoto Conference of Advanced Medicine of Ophthalmology in Tokyo (WACAMOTO)
    • Related Report
      2017 Research-status Report
  • [Book] 実験医学増刊:脂質クオリティ2018

    • Author(s)
      畑 匡侑、池田 華子
    • Total Pages
      246
    • Publisher
      羊土社
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] クリスタリン網膜症の処置および/または予防方法2017

    • Inventor(s)
      畑匡侑・池田華子
    • Industrial Property Rights Holder
      畑匡侑・池田華子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Acquisition Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] クリスタリン網膜症の処置および/または予防方法2017

    • Inventor(s)
      畑 匡侑、池田華子
    • Industrial Property Rights Holder
      国立大学法人 京都大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-090296
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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