Analysis of retinal degeneration caused by dysfunction of ubiquitin proteasome system

• Project/Area Number: 25462702
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Hokkaido 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: ¥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.

Research Products

• [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
• [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
  • Peer Reviewed / Open Access
• [Journal Article] Oxidative stress in the levator aponeurosis in Asian involutional blepharoptosis (2014)
  • 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
  • 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
  • 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）
• [Presentation] Decreased Proteasomal Activity Causes Retinal Degeneration in Mice (2013)
  • 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)