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Investigation of the molecular mechanism of glaucoma and gene therapy for the treatment of glaucoma

Research Project

Project/Area Number 10470362
Research Category

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

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

Principal Investigator

KASHII Satoshi (1999-2000)  Kyoto University Graduate School of Medicine, Department of Ophthalmology & Visual Sciences, Assistant Professor, 医学研究科, 助教授 (50194717)

谷原 秀信 (1998)  京都大学, 医学研究科, 講師 (60217148)

Co-Investigator(Kenkyū-buntansha) TAKAHUSHI Masayo  Kyoto University Graduate School of Medicine, Department of Ophthalmology & Visual Sciences, Instructor, 医学研究科, 助手 (80252443)
柏井 聡  京都大学, 医学研究科, 講師 (50194717)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2000: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥4,400,000 (Direct Cost: ¥4,400,000)
Keywordsglaucoma / retinal ganglion cell / neuroprotective therapy / neuroregenerative therapy / CNTF / BDNF / neurocan / phosphacan / アポトーシス / NMDA / 神経防御 / バイグリカン / ラミニン / カイニン酸 / IL-1 / TGFβ_2 / 房水 / プロテオグリカン / 線維柱帯細胞 / サル緑内障モデル眼 / 遺伝子導入
Research Abstract

In glaucomatous eyes, abnormally increased intraocular pressure (IOP) induces retinal ganglion cell death, resulting in loss of visual acuity. At present, most of the drugs and surgeries for glaucoma have been developed for lowering IOPs. Our experimental studies are aimed to protect the cell death of retinal ganglion cells, "neuroprotective therapy, "and repair the damaged axons, "neuroregenerative therapy." In an attempt to rescue retinal ganglion cells from cell death, we investigated the neuroprotective effects of neurotrophic factors in animal glaucomatous models. Our immunohistochemical analyses showed that, in the retinal tissues of animal glaucomatous models, Muller glial cells and astrocytes were activated, and one of neurotrophic factors, ciliary neurotrophic factor (CNTF), was secreted from these glial cells. Moreover, two types of neurotrophic factors, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) showed neuroprotective effects for retinal ganglion cells in animal glaucomatous models. In addition, we demonstrated that two types of chondroitin sulfate proteoglycans (CSPGs), neurocan and phosphacan, were highly expressed in the developing retina. Furthermore, the CSPGs regulated the neurite outgrowth from retinal ganglion cells in vitro, indicating the possibility that the neuroregenerative therapy can be achieved by controlling the expression of the CSPGs. Our investigations will play important roles in developing the new concepts of the treatment for glaucoma.

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Honjo M et al.: "Expression of ciliary neurotrophic factor by activatal retinal Muller cells in eyes with NMDA-and kainic acid-induced neuronal death"Investigative Ophthalmology & Visual Science. 41. 552-560 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honjo M et al.: "Differential expression of cadherin adhesion receptors in the neural retina of the postnatal mouse"Investigative Ophthalmology & Visual Science. 41. 546-551 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inatani M et al.: "Spatiotemporal expression patterns of 6B4 proteorlycan/phosphacan in the developing rat retina."Investigative Ophthalmology & Visual Science. 41. 1990-1997 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inatani M et al.: "Upregulated expression of neurocan, a nervous-tissue specific proteoglycan, in transient retinal ischemia."Investigative Ophthalmology & Visual Science. 41. 2748-2754 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kido N et al.: "Neuroprotective effects of brain-derivedneurotrophic factor in eyes with NMPA-induced neuronal death."Brain Research. 24. 59-67 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inatani M et al.: "Neuroglycan C, a neuroal tissue-specific transmembrane chondroitin sulfate proteoglycan, in retinal neural network formation."Investigative Ophthalmology & Visual Science. 41. 4338-4346 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honjo M, Tanihara H, Kido N, Inatani M, Okazaki K, Honda Y: "Expression of ciliary neurotrophic factor by activated retinal Muller cells in eyes with NMDA-and kainic acid-induced neuronal death."Investigative Ophthalmology & Visual Science. 41. 552-560 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honjo M, Tanihara H, Suzuki S, Tanaka T, Honda Y, Takeichi M: "Differential expression of cadherin adhesion receptors in the neural retina of the postnatal mouse."Investigative Ophthalmology & Visual Science. 41. 546-551 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inatani M, Tanihara H, Oohira A, Honjo M, Honda Y: "Spatiotemporal expression patterns of 6B4 proteoglycan/phosphacan in the developing rat retina."Investigative Ophthalmology & Visual Science. 41. 1990-1997 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inatani M, Tanihara H, Oohira A, Honjo M, Kido N, Honda Y: "Upregulated expression of neurocan, a nervous-tissue specific proteoglycan, in transient retinal ischemia."Investigative Ophthalmology & Visual Science. 41. 2748-2754 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kido N, Tanihara H, Honjo M, Inatani M, Tatsuno T, Nakayama C, Honda Y: "Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death."Brain Research. 24. 59-67 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inatani M, Tanihara H, Oohira A, Otori Y, Nishida A, Honjo M, Kido N, Honda Y: "Neuroglycan C, a neural tissue-specific transmembrane chondroitin sulfate proteoglycan, in retinal neural network formation."Investigative Ophthalmology & Visual Science. 41. 4338-4346 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Inatani et.al.: "Neuroglycan C.a neural tissue-specific transmembrane chondroitin sulfate proteoglycan in retinal neural network formation"Invest Ophthalnol Vis Sci. 41-13. 4338-4346 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Kido et.al: "Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death"Brain Res. 884. 59-67 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Inatani et.al: "Upregulated expression of neurocan : a nervous tissue specific proteoglycan in transient retinal ischemia"Invest Ophthalmol Vis.Sci. 41-9. 2748-2754 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Inatani et al.: "Spatiotemporal expression patterns of 6B4 proteoglycanl phosphacan in the developing rat retina"Invest Ophtalmol Vis Sci. 41-7. 1990-1997 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Honjo et.al: "Expression of ciliary neurotrophic factor activated by retinal Muller cells in eyes with NMDA-and kainic acid-induced neuronal death."Invest.Ophtalmol Vis.Sci. 41-2. 552-560 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inatani M et al.: "Identitication of a brain-specific chondroitin sulfate proteglycan, neurocan, in rat retina"Inrest. Ophthalmol. & Vis. Sci.. 40. S480 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanihara H.et al.: "Expression of protenglycan decolin in neural retina"Invest. Ophthalmol & Vis. Sci.. 40. S480 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kido N.et al.: "Neuroprotective effects of brain-derived neurotrophic factor (BDNF) in eyes with glutamerte receptor-mediated neuronal death"Invest. Ophthalmol. & Vis. Sci.. 40. S131 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honjo M.et al.: "Up-regulated expression of ciliary neurotrophic factor in Maller cells in response to stutanate receptor-mediated neuronal death"Invest. Ophthalmol & Vis. Sci.. 40. S131 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okazaki et al.: "Changed cellular behavicrs of cultured human trabecular meshwork cells in response to cytokines"Invest Ophthalmol & Vis. Sci.. 40. S506 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanihara H他: "Changed Gene Expression in the Retina of Primate Eyes with Experimental Glaucona" Invest.Ophthalmol.Vis.Sci.39・4. 30-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okazaki K他: "Facilitated Introduction of DNA and Oligonucleotides into Primate Trabeallar Meshwork Cells by HVJ Liposone Methods" Invest.Ophthalmol.Vis.Sci.39・4. 30-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Muto T他: "Transforming Growth Factor-β2 Up-regulated Expression of Proteoglycar Decorin in Trabecular Meshwork Cells" Invest.Ophthalmol.Vis.Sci.39・4. 482-482 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hangai M他: "Invitro Dirivery of Phesphorothioate Oligonucleotides into Murine Retina." Arch.Opthalmol.116・3. 342-348 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hangai M他: "Introduction of DNA into Rat and Primate Trabecular Meshwork by fusogenic Liposomes." Invest.Ophthalmol.Vis.Sci.39・4. 509-516 (1998)

    • Related Report
      1998 Annual Research Report

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

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