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Elucidation of molecular mechanism and treatment strategy to reverse lens opacity

Research Project

Project/Area Number 17K11470
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionKanazawa Medical University

Principal Investigator

KUBO ERI  金沢医科大学, 医学部, 教授 (10262619)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords白内障 / Peroxiredoxin 6 / 酸化ストレス / Shumiya Cataract Rat / ラノステロール / 眼細胞生物 / Shimiya Cataract Rat / Peroxiredoxin 6 / 眼細胞生物学 / 眼科学
Outline of Final Research Achievements

In this study, we found that lens proteins were insolubilized in cataracts of hereditary Shumiya Cataract Rats (SCRs). DNA microarray analysis of lens epithelial cells (LECs) revealed that the expression of genes related with lens fiber differentiation, antioxidant and regulation of osmolarity, which are required for maintaining lens transparency were decreased. Administration of antioxidant protein, sumoylation (SUMO)-deficient Peroxiredoxin (Prdx6) recombinant protein, enhanced the anti-oxidative ability in cultured human LEC, and delayed the onset of cataract in SCR after subconjunctival injection. Therefore, administration of SUMO-deficient Prdx6 may prevent cataract progression.

Academic Significance and Societal Importance of the Research Achievements

白内障は世界の中途失明原因第一位の疾患である。現在は、手術が唯一の治療法であり、有効な白内障薬物治療はない。また、有効な加齢白内障動物モデルがないため、薬物治療の開発研究が難航することが多い。本研究結果より、加齢白内障動物モデルとしてのShumiya Cataract Ratの有用性が明らかになった。また、加齢白内障の主原因の一つである酸化ストレスを抑制する抗酸化タンパクPrdx6が、SCR白内障を遅延させることが明らかになった。よって、Prxx6が、ヒト加齢白内障の進行を遅らせ、手術加療が必要となる時期を遅らせることができる可能性がある。

Report

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

    (3 results)

All 2019

All Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Gene expression profiling of lens epithelial cells in Shumiya cataract rats2019

    • Author(s)
      Eri Kubo, Hidetoshi Ishida, Shinsuke Shibata, Teppei Shibata, Yuka Nakamura , Yasuhito Ishigaki , Dhirendra P Singh, Hiroshi Sasaki
    • Organizer
      ARVO annual meeting
    • Related Report
      2019 Annual Research Report
  • [Presentation] Shumiya Cataract Rat白内障の遺伝子発現変化の網羅的解析2019

    • Author(s)
      石田秀俊、柴田哲平、柴田伸亮、中村有香、石垣靖人、佐々木洋、久保江理
    • Organizer
      第58回日本白内障学会総会/第45回水晶体研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Gene expression profiling of lens epithelial cells in Shumiya cataract rats2019

    • Author(s)
      Kubo E
    • Organizer
      ARVO 2019 Annual Meeting
    • Related 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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