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Development of new method for optic nerve regeneration-a combined approach of the peripheral nerve transplant and intraocular injection of neurotrophins.

Research Project

Project/Area Number 06557091
Research Category

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

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionOsaka University

Principal Investigator

FUKUDA Yutaka  Department of Physiology, Osaka University Medical School, Professor., 医学部, 教授 (90028598)

Co-Investigator(Kenkyū-buntansha) SAWAI Hajime  Department of Welfare and Health Science, Okayama Prefectural University, Associ, 保健福祉学部, 助教授 (20202103)
KASAKA Jun  Department of Physiology, Osaka University Medical School, Assistant Professor., 医学部, 助手 (40243216)
NOMURA Shintaro  Department of Pathology, Osaka University Medical School, Associate Professor., 医学部, 助教授 (80159087)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1995: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1994: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsneurotrophin / axonal regeneration / retinal ganglion cells / monoclonal antibody C38 / neurotrophin receptor / in situ hybridization / peripheral nerve transplantation / clinical application / retinal ganglion / Y79 / BDNF(brain derived neurtrophic factor) / PCR(polymerase chain reaction) / transfection
Research Abstract

In mammals, retinal ganglion cells can not regenerate their axons after axotomy and their somas suffer from retrograde cell death. With peripheral nerve graft, however, axons of retinal ganglion cells can regrow through the grafted nerve. So far the number of regrowing axons is reported to be less than 5% of the total optic nerve fibers. To enhance cell servival and axonal regeneration of axotomized retinal ganglion cells, we tried to examine the effects of intraocular injections of various neurotrophins on cell survival and axonal regeneration in combination with the peripheral nerve graft. We made the following findings : (1) Intraocular injection of brain derived neurotrophic factor (BDNF) promotes axonal regrowth of retinal ganglion cells withih the retina but it is not effective for these intraretinal axons to penetrate into the optic nerve, suggesting existence of some non-permissive molecules around the optic disc. (2) Thus, the intraocular injections of BDNF in combination with the peripheral nerve graft was not effective to improve the number of ganglion cells with regenerated axons into the graft. (3) Low affinity NGF receptor (LNGFR) and some neurotophin receptor mRNAs were localized in subpopulations of retinal ganglion cells. (4) The surviving retinal ganglion cells without regenerating axons could be distinguished from those with regenerated axons by immunostaining with the monoclonal antibody C38 that we have recently isolated.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Fukuda,Y,et al: "Axonal regeneration of cat's retinal ganglion cells by peripheral nerve transplant." Biomedical Research. Suppl.1. 123-125 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watanabe M,et al: "Myelination of regenerated optic fibers in peripheral nerve graft of adult cats." Experimental Brain Research. 98. 39-43 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kosaka J.et al: "Expression and localization of γ-Aminobutyric Acid A (GABA_A) Receptor α1 subunit and L-Glutamate Decarboxylase (GAD) mRNAs in rat retina : an analysis by in situ hybridization." Molecular Brain Research. 25. 163-167 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Morii E.et al: "Demonstration of retinal cells expressing messenger RNAs of the c-kit receptor and its ligand." Neuroscience Letters. 166. 168-170 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hirata T,et al: "Characterization of c-Kit-positive neurons in the dorsal root ganglion of mouse." Developmental Brain Research. 85. 201-211 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watanabe M,et al: "Number and dendritic morphology of retinal ganglion cells that survived after axotomy in adult cats." Journal of Neurobiology. 27. 189-203 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masu M,et al: "Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene." Cell. 80. 757-765 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sauve Y,et al: "Functional synaptic connections made by regenerated retinal ganglion cell axons in the superior colliculus of adult hamsters." Journal of Neuroscience. 15. 665-675 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Sawai H,et al: "Functional and morphological restoration of intracranial brachial lesion of the retinocollicular pathway by peripheral nerve autografts in adult hamsters." Experimental Neurology. 137. 94-104 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Wakabayashi T,et al: "Monoclonal antibody C38 recognizes retinal ganglion cells in cats and rats." Vision Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Wakabayashi T,et al: "Monoclonal antibody C38 lebels surviving retinal ganglion cells after peripheral nerve graft in axotomized rat retina." Brain Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Eiichi Morii, Jun Kosaka, Shintaro Nomura, Yutaka Fukuda, and Yukihiko Kitamura.: "Demonstration of retinal cells expressing messenger RNAs of the c-kit receptor and its ligand." Neurosci.Lett.166. 168-170 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masami Watanabe, Hajime Sawai and Yutaka Fukuda.: "Myelination of regenerated optic fibers in peripheral nerve graft of adult cats." Exp.Brain Res.98. 39-43 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masayuki Yamashita, Yukiko Yoshimoto and Yutaka Fukuda.: "Muscarinic acetylcholine responses in the early embryonic chick retina." J.Neurobiol. 25. 1144-1153 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Jun Kosaka, Eiichi Morii, Masato Taniguchi, Yukihiko Kitamura, Shintaro Nomura and Yutaka Fukuda.: "Expression and localization of gamma-aminobutyric acid A (GABA_A) receptor alpha1 subunit and L-glutamate decarboxylase (GAD) mRNAs in rat retina : an analysis by in situ hybridization." Mol.Brain Res.25. 163-167 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Kaisho, M.Miyamoto, O.Shino, H.Onoue, Yukihiko Kitamura and Shintaro Nomura: "Expression of neurotrophin gene in the brain of senescence-accelerated mouse (SAM) during postnatal development." Brain Res.647. 139-144 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masami Watanabe, Hajime Sawai and Yutaka Fukuda.: "Number and dendritic morphology of retinal ganglion cells that survived after axotomy in adult cats." J.Neurobiol.27. 189-203 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Miho Sugioka, Hajime Sawai, Eijiro Adachi and Yutaka Fukuda.: "Changes of compound action potentials in retrograde axonal degeneration of rat optic nerve." Exp.Neurol.132. 262-270 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yves Sauve, Hajime Sawai and Michael Rasminsky.: "Functional synaptic connections made by regenerated retinal ganglion cell axon in the superior colliculus of adult hamsters." J.Neurosci.15. 665-675 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hajime Sawai, Miho Sugioka, Katsuko Morigiwa, Hitoshi Sasaki, Kwok-Fai So and Yutaka Fukuda.: "Functional and morphological restoration of intracranial brachial lesion of the retinocollicular pathway by peripheral nerve autografts in adult hamsters." Exp.Neurol.137. 94-104 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taketoshi Wakabayashi, Yutaka Fukuda and Jun Kosaka.: "Monoclonal antibody C38 recognizes retinal ganglion cells in cats and rats." Vision Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taketoshi Wakabayashi, Yutaka Fukuda and Jun Kosaka.: "Monoclonal antibody C38 labels surviving retinal ganglion cells after peripheral nerve graft in axotomized rat retina." Brain Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hajime Sawai, David B Clarke, Pavla Kittelova, Garth M.Bray and Albert J.Aguayo.: "Brain derived neurotrophic factor and neurotrophin-4/5 stimulate growth of axonal branches from regenerating retinal ganglion cells." J.Neurosci.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watanabe M,et al: "Number and dendritic morphology of retinal ganglion cells that survived after axotomy in adult cats." Journal of Neurobiology. 27. 189-203 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masu M, et al: "Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene." Cell. 80. 757-765 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] SauveeY、 et al: "Functional synaptic connections made by regenerated letinal ganglion cell axons in the superior colliculus of adult hamsters." Journal of Neuroscience. 15. 665-675 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sawai H, et al: "Functional and morphological restoration of intracranial brachial lesion of the retinocollicular pathway by peripheral nerve autografts in adult hamsters." Experimental Neurology. 137. 94-104 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Wakabayashi T, et al: "Monoclonal antibody C38 recognizes retinal ganglion cells in cats and rats." Vision Research. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Wakabayashi T, et al: "Monoclonal antibody C38 labels surviving retinal ganglion cells after peripheral nerve graft in axotomized rat retina." Brain Research. (in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Masu M,et al.: "Specific deficient of the ON response in visual transmission by targeted disruption of the mGluR6 gene." Cell. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Fukuda Y,et al: "Axonal regeneration of cat's retinal ganglion cells by peripheral nerve transplant." Biomedical Research. 15Spp1.1. 123-1125 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Watanabe,M.et al: "Myelination of regenerated optic fibers in peripheral nerve graft of adult cats." Experimental Brain Research. 98. 39-43 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hirata T,et al: "Characterization of c-Kit-positive neurons in the dorsal root ganglion of mouse." Developmental Brain Research. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Kosaka J,et al: "Expression and localization of γ-Aminobutyric Acid A(GABA_A)Receptor α 1 subunit and L-Glutamate Decarboxylase(GAD)mRNAs in rat retina:" Molecualr Brain Research. 25. 163-167 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Morii E,et al: "Demonstration of retinal cells expressing messenger RNAs of the c-kit receptor and its ligand." Neuroscience Letters. 166. 168-170 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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