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MOLECULAR MECHIANISM OF RETINAL GANGLION CELL APOTPTOSIS ANDEXPERIMENTAL GENE THERAPRYTO PREVENT THE CELL DEATH

Research Project

Project/Area Number 10470361
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionSHINSHU UNIVERSITY

Principal Investigator

YOSHIMURA Nagahisa  DEPARTMENT OF OPHTHALMOLOGY, SHINSHU UNIVERSITY, PROFESSSOR, 医学部, 教授 (70211662)

Co-Investigator(Kenkyū-buntansha) KIKUKCHI Takanobu  RESEARCH INSTITUTE FOR INSTRUMENTAL ANALYSIS, ASSOCIATE PROFESSOR, 機器分析センター, 助教授 (50177797)
栗本 康夫  信州大学, 医学部・附属病院, 講師 (50293519)
海平 淳一  信州大学, 医学部附属病院, 講師 (80193928)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1998: ¥5,400,000 (Direct Cost: ¥5,400,000)
KeywordsRETINAL GANGLION CELLS / CELL DEATH / NEUROPROTECTION / CASPASE / C-JUN / BDNF / caspase / c-jun / NOS / 細胞神経節細胞 / Caspase / C-Jun
Research Abstract

(1) Research on rat retinal cell death following ischemia-reperfusion
WE have shown that caspase-3 plays an important role in the inner retina, whereas caspase-1 was more important in the outer retina.
Horizontal cells that express p16INK4 did not show apoptotic features but were necrotic but amacrine cells that do not express the gene were apoptotic.
Reactive oxygen species played an important role in retinal ischemia-reperfusion injury.
(2) Research on retinal ganglion cell apoptosis
Retinal ganglion cells dying by apoptosis expressed c-jun and such cell also expressed caspase-2. Caspases-1 and -3 were not expressed dying retinal ganlion cells. BDNF treatment decreased the number of apoptotic cells but expression of c-jun was not different from without the treatment. Caspase-2 expression was decreased by the treatment.
(3) Experimental gene therapy for RCS rats
Treatment of RCS rats with AAV-Bcl-xL was effective to reduce the visual cell damage found in the RCS rats.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Kuroiwa S,Katai N,Shibuki H,Yoshimura N. et al.: "Expression of cell cycle-related genes in dying cells following retinal ischemic injury in the rat."Invest Ophthalmol Vis Sci.. 39. 610-617 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuki H,Katai N,Kuroiwa S,Kurokawa T,Yodoi J,and Yoshimura N.: "Protective effect of adult T cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat."Invest Ophthalmol Vis Sci.. 39. 1470-1477 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurokawa T,Katai N,Kurimoto Y,and Yoshimura N.: "BDNF diminishes caspase-2 but not of c-Jun in retinal ganglion cells after ischemia-reperfusion injury."Invest Ophthalmol Vis Sci. 40. 3006-3011 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kuroiwa S,Katai N,and Yoshimura N.: "Apoptosis and necrosis in retinal ischemia-reperfusion injury : A possible role of p16^<INK4> in the determination of cell death."Invest Ophthalmol Vis Sci.. 40. 528-533 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katai N,Kikuchi T,Shibuki H,Kuroiwa S,Arai J,Kurokawa T,and Yoshimura N.: "Caspase-like proteases activated in apoptotic photoreceptors of Royal College of Surgeons rat."Invest Ophthalmol Vis Sci.. 40. 2697-2705 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuki H,Katai N,Yodoi J,Uchida K,and Yoshimura N.: "Lipid peoxidation and peroxynitrite in retinal ischema-reperfusion injury."Invest Ophthalmol Vis Sci. 41. 3607-3614 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kuroiwa S, Katai N, Shibuki H, Kurokawa T, Yoshimura N.et al.: "Expression of cell cycle-related genes in dying cells following retinal ischemic injury in the rat."Invest Ophthalmol Vis Sci.. 39. 610-617 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuki H, Katai N, Kuroiwa S, Kurokawa T, Yodoi J, and Yoshimura N.: "Protective effect of adult T cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat."Invest Ophthalmol Vis Sci.. 39. 1470-1477 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kuroiwa S, Katai N, and Yoshimura N.: "Apoptosis and necrosis in retinal ischemia-reperfusion injury : A possible role of p16^<INK4> in the determination of cell death."Invest Ophthalmol Vis Sci.. 40. 528-533 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katai N, Kikuchi T, Shibuki H, Kuroiwa S.Arai J, Kurokawa T, and Yoshimura N.: "Caspase-like proteases activated in apoptotic photoreceptors of Royal College of Surgeons rat."Invest Ophthalmol Vis Sci.. 40. 1802-1807 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katai N, and Yoshimura N.: "Apoptotic retinal neuronal death by ischemia-reperfusion is executed by two distinct caspase family proteases."Invest Ophthalmol Vis Sci.. 40. 2697-2705 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurokawa T, Katai N, Kurimoto Y, and Yoshimura N.: "BDNF diminishes caspase-2 but not of c-Jun in retinal ganglion cells after ischemia-reperfusion injury."Invest Ophthalmol Vis Sci.. 40. 3006-3011 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuki H, Katai N, Yodoi J, Uchida K, and Yoshimura N.: "Lipid peoxidation and peroxynitrite in retinal ischema-reperfusion injury."Invest Ophthalmol Vis Sci.. 41. 3607-3614 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kuroiwa S,Katai N,Shibuki H,Yoshimura N. et al.: "Expression of cell cycle-related genes in dying cells following retinal ischemic injury in the rat."Invest Ophthalmol Vis Sci.. 39. 610-617 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shibuki H,Katai N,Kuroiwa S,Kurokawa T,Yodoi J,and Yoshimura N.: "Protective effect of adult T cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat."Invest Ophthalmol Vis Sci.. 39. 1470-1477 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kurokawa T,Katai N,Kurimoto Y,and Yoshimura N.: "BDNF diminishes caspase-2 but not of c-Jun in retinal ganglion cells after ischemia-reperfusion injury."Invest Ophthalmol Vis Sci. 40. 3006-3011 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kuroiwa S,Katai N,and Yoshimura N.: "Apoptosis and necrosis in retinal ischemia-reperfusion injury : A possible role of p16^<INK4> in the determination of cell death."Invest Ophthalmol Vis Sci.. 40. 528-533 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katai N,Kikuchi T,Shibuki H,Kuroiwa S,Arai J,Kurokawa T,and Yoshimura N.: "Caspase-like proteases activated in apoptotic photoreceptors of Royal College of Surgeons rat."Invest Ophthalmol Vis Sci.. 40. 2697-2705 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shibuki H,Katai N,Yodoi J,Uchida K,and Yoshimura N.: "Lipid peoxidation and peroxynitrite in retinal ischema-reperfusion injury."Invest Ophthalmol Vis Sci. 41. 3607-3614 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hangai M, Yoshimura N et al: "Roles of constitutive nitric oxide synthase in post-ischemic rat retsna"Invest Ophthalmol Vis Sci. 40. 450-458 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kuroiwa S, Yoshimura N et al: "Apoptosis and necrisis in retinal ischemic reperfusion injury"Invest Ophthalmol Vis Sci. 40. 528-533 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Katai N, Yoshimura N: "Apoptotic ratinol neuronal death by ischemia-repefusion is executed by two distinot caspase protoases"Invest Ophthalmol Vis Sci. 40. 2697-2705 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kurokawa T. Yoshimura N et al: "BDNF diminishes cospage-2 but not of c-jun in retinol ganglion cells after ischemia-reperfusion injury"Invest Ophthalmol Vis Sci. 40. 3006-3011 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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