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Analysis of retinal degeneration caused by dysfunction of ubiquitin proteasome system

Research Project

Project/Area Number 25462702
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionHokkaido University

Principal Investigator

NODA Mika  北海道大学, 医学(系)研究科(研究院), 客員研究員 (10296668)

Co-Investigator(Kenkyū-buntansha) NODA Kousuke  北海道大学, 大学院医学研究科, 准教授 (90296666)
TOMARU Utano  北海道大学, 大学院医学研究科, 准教授 (20360901)
OZAWA Yoko  慶應義塾大学, 医学部(信濃町), 講師 (90265885)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsプロテアソーム / 網膜色素変性 / 視細胞死 / アポトーシス
Outline of Final Research Achievements

Recent studies have revealed that ubiquitin proteasome system (UPS) dysfunction is involved in the pathogenesis of systemic neurodegenerative diseases such as Alzheimer’s disease. In ocular diseases, retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal neurodegenerative disorders characterized by progressive degeneration of photoreceptors. Therefore, whether impairment of UPS function also causes RP has been of great interest.
In the present study, using an animal model of decreased proteasomal activity (β5t-Tg mice) we demonstrated that i) decreased function of proteasome causes retinal degeneration in vivo, largely attributed to photoreceptor cell death, and ii) photoreceptor cells are vulnerable to the functional disturbance of proteasome in the retina. The current data raise an interesting question regarding the impact of proteasome dysfunction in the pathogenesis of RP.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2015 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results)

  • [Journal Article] 感覚網膜におけるプロテアソーム機能不全の影響2015

    • Author(s)
      安藤 亮、野田航介、外丸詩野、鴨下 衛、小沢洋子、納富昭司、久冨智朗、野田実香、神田敦宏、石橋達朗、笠原正典、石田 晋
    • Journal Title

      北海道医学雑誌

      Volume: 90 Pages: 136-136

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Decreased proteasomal activity causes photoreceptor degeneration in mice.2014

    • Author(s)
      Ando R, Noda K, Tomaru U, Kamoshita M, Ozawa Y, Notomi S, Hisatomi T, Noda M, Kanda A, Ishibashi T, Kasahara M, Ishida S.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 55 Issue: 7 Pages: 4682-4690

    • DOI

      10.1167/iovs.13-13272

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxidative stress in the levator aponeurosis in Asian involutional blepharoptosis2014

    • Author(s)
      Kase S, Noda M, Yoshikawa H, Yamamoto T, Ishijima K, Ishida S
    • Journal Title

      Ophthal Plast Reconstr Surg

      Volume: 30 Issue: 4 Pages: 290-294

    • DOI

      10.1097/iop.0000000000000090

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of vascular endothelial growth factor in human ocular adnexal lymphoma.2014

    • Author(s)
      Kinoshita S, Kase S, Ando R, Dong Z, Fukuhara J, Dong Y, Takashina S, Noda K, Noda M, Kanda A, Ishida S.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 55 Issue: 6 Pages: 3461-3467

    • DOI

      10.1167/iovs.13-13510

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ユビキチンプロテアソーム系機能不全による網膜変性2013

    • Author(s)
      安藤 亮、野田航介、外丸詩野、野田実香、高階沙織、董 陽子、木下哲志、福原淳一、董震宇、神田敦宏、石田 晋
    • Organizer
      第117回 日本眼科学会
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] Decreased Proteasomal Activity Causes Retinal Degeneration in Mice2013

    • Author(s)
      Ryo Ando, Kousuke Noda, Utano Tomaru, Mamoru Kamoshita, Yoko Ozawa, Shoji Notomi, Toshio Hisatomi, Atsuhiro Kanda and Susumu Ishida
    • Organizer
      Association for Research in Vision and Ophthalmology
    • Place of Presentation
      Washington State Convention Center (Seattle, USA)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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