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A new model of retinal photoreceptor cell degeneration induced by a chemical hypoxia-mimicking agent, cobalt chloride : clarification of its mechanism and protection of retinal degeneration

Research Project

Project/Area Number 19590243
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionGifu University

Principal Investigator

NIWA Masayuki  Gifu University, 医学部, 教授 (40156146)

Co-Investigator(Kenkyū-buntansha) HARA Akira  岐阜大学, 大学院・医学系研究科, 教授 (10242728)
AOKI Hitomi  岐阜大学, 大学院・医学系研究科, 助教 (10550361)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords網膜視細胞障害 / CoCl2 / 実験動物モデル / Apoptosis / 予防・治療・再生 / CoC12 / 予防、治療、再生 / 中枢神経 / 網膜神経障害 / 視細胞
Research Abstract

マウス・ラットにおけるCoCl2(Co)の選択的網膜視細胞障害能を詳細に検討し、その細胞死がapoptosisによるものであることを明らかにするとともに、Coの至適投与量を決定することにより、視細胞障害モデルを確立し、網膜障害予防・治療の検討に有用であることを明かにした。視細胞障害発現機序としては、視細胞層へのカルシウムの特異的な集積が観察され、カルシウム濃度の局在変化によるメカニズムの関与が示唆された。脳虚血モデルに対し有効性を示すラジカル消去剤PBNを用い、Co誘発障害モデルでの有効性を組織化学的に検討したところ比較としたNMDA誘発神経節細胞死はPBNにより有意に、用量依存的に抑制されたが、Coによる障害に対しては改善が認められなかった。このことからCoによる視細胞障害性にはラジカルの関与が否定的である事が示唆された。ERG、VEPへの影響を検討したところ、NMDA同様Co投与によりそれらの発生が顕著に抑制された。なお、NMDA投与によるERGの抑制はラジカル消去剤PBNにより回復が認められたが、Coによる抑制には回復は認められなかった。再生治療への応用の目的でマウスES細胞をCoあるいはNMDA誘発網膜細胞障害モデルに移植し、再生治療を試みた。ES細胞は移植により網膜神経節細胞層に浸潤するような形で生着し、この生着率はNMDA処理後の障害網膜では非処置群に比べ増加した。さらにこの生着細胞の腫瘍化はmethotrexateの併用による制御の可能性が示唆された。一方、Co障害後へのES細胞の移植を試みたところ、有意な生着率の増加は観察されなかった。今後ヒト由来人工多能性幹細胞(iPS細胞)を用いて同様な移植の検討を試みる。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (23 results)

All 2009 2008 2007

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (7 results) Book (3 results)

  • [Journal Article] Spatiotemporal expression of Hsp20 and its phosphorylation in hippocampal CAl pyramidal neurons after transient forebrain ischemia.2009

    • Author(s)
      Niwa M, Hara A, Taguchi A, Aoki H, Kozawa 0, Mori H.
    • Journal Title

      Neurol Res. (掲載確定)(Epub ahead of print)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatiotemporal expression of Hsp20 and its phosphorylation in hippocampal CA1 pyramidal neurons after transient forebrain ischemia2008

    • Author(s)
      Niwa M, Hara A, Taguchi A, Aoki H, Kozawa O, Mori H.
    • Journal Title

      Neurol Res (Epub ahead of print)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Localization and spatiotemporal expression of IDO following transient forebrain ischemia in gerbils2008

    • Author(s)
      Taguchi A, Hara A, Saito K, Hoshi M, Niwa M, Seishima M, Mori H.
    • Journal Title

      Brain Res 1217

      Pages: 78-85

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neuron-like differentiation and selective ablation of undifferentiated embryonic stem cells containing suicide gene with Oct-4 promoter2008

    • Author(s)
      Hara A, Aoki H, Taguchi A, Niwa M, Yamada Y, Kunisada T, Mori H.
    • Journal Title

      Stem Cells Dev. 17

      Pages: 619-627

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transplantation of cells from eye-like structures differentiated from embryonic stem cells in vitro and in vivo regeneration of retinal ganglion-like cells2008

    • Author(s)
      Aoki H, Hara A, Niwa M, Motohashi T, Suzuki T, Kunisada T.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol 246

      Pages: 255-265

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transplantation of cells from eye-like struetures differentiated from embryonic stem cells in vitro and in vivo regeneration of retinal ganglion-like cells.2008

    • Author(s)
      Aoki H, Hara A, Niwa M, Motohashi T, Suzuki T, Kunisada T.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol. 246

      Pages: 255-265

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuron-like differentiation and selective ablation of undifferentiated embryonic stem cells containing suic idegene with Oct-4 promoter.2008

    • Author(s)
      Hara A, Aoki H, Taguchi A, Niwa M, Yamada Y, Kunisada T, Mori H.
    • Journal Title

      Stem Cells Dev. 17

      Pages: 619-627

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localization and spat iotemporal expression of IDO following transient forebrain ischemia in gerbils.2008

    • Author(s)
      Taguchi A, Hara A, Saito K, Hoshi M, Niwa M, Seishima M, Mori H.
    • Journal Title

      Brain Res. 1217

      Pages: 78-85

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localization of septin 8 in murine retina, and spatiotemporal expression of septin 8 in a murine model of photoreceptor cell degeneration2007

    • Author(s)
      Hara A, Taguchi A, Niwa M, Aoki H, Yamada Y, Ito H, Nagata K, Kunisada T, Mori H.
    • Journal Title

      Neurosci Lett 423

      Pages: 205-210

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] An in vitro mouse model for retinal ganglion cell replacement therapy using eye-like structures differentiated from ES cells2007

    • Author(s)
      Aoki H, Hara A, Niwa M, Motohashi T, Suzuki T, Kunisada T.
    • Journal Title

      Exp Eye Res 84

      Pages: 868-875

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] An in vitro mouse model for retinal ganglion cell replacement therapy using eye-like structures differentiated from ES cells.2007

    • Author(s)
      Aoki H, Hara A, Niwa M, et. al.
    • Journal Title

      Exp Eye Res. 84

      Pages: 868-875

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localization of septin 8 in murine retina, and spatiotemporal expression of septin 8 in a murine model of photoreceptor cell degeneration.2007

    • Author(s)
      Hara A, Taguchi A, Niwa M, et. al.
    • Journal Title

      Neurosci Lett. 423

      Pages: 205-210

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transplantation of cells from eye-like structures differentiated from embryonic stem cells in vitro and in vivo regeneration of retinal ganglion-like cells2007

    • Author(s)
      Aoki H, Hara A, Niwa M, et. al.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol. 246

      Pages: 255-265

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] CoCl2による選択的視神経障害モデルの確立2009

    • Author(s)
      Niwa M, Aoki H, Kozawa O, Hara A.
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2008 Final Research Report
  • [Presentation] CoC12による選択的視神経障害モデルの確立2009

    • Author(s)
      Niwa M, Aoki H, Kozawa 0, Hara A.
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] 眼球の前房における免疫特権を活かしたマウスES細胞由来色素細胞の移植による虹彩の有色化とin vivoにおける分化制御2008

    • Author(s)
      青木仁美、丹羽雅之、原明、國貞隆弘
    • Organizer
      第29回日本炎症・再生医学会
    • Place of Presentation
      東京
    • Year and Date
      2008-07-10
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] 一過性脳虚血に伴う海馬遅発性神経細胞死におけるHsp20の発現とそのリン酸化.2008

    • Author(s)
      丹羽雅之、原 明、田口紋子, ら
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] マウス胚性幹細胞由来眼様構造の移植による網膜神経節細胞の再生2007

    • Author(s)
      青木仁美、丹羽雅之、原 明, ら
    • Organizer
      第28回日本炎症・再生医学会
    • Place of Presentation
      東京
    • Year and Date
      2007-08-02
    • Related Report
      2007 Annual Research Report
  • [Presentation] Transplantation of eye-like structures differentiated from ES cells in vitro and the resultant regeneration of retinal ganglion cells in vivo.2007

    • Author(s)
      Aoki H, Hara A, Niwa M, et. al.
    • Organizer
      ARVO 2007
    • Place of Presentation
      Florida
    • Year and Date
      2007-05-09
    • Related Report
      2007 Annual Research Report
  • [Presentation] 試験管内で分化誘導されたマウス胚性(mES)細胞由来眼様構造の成体マウスへの移植と網膜神経節細胞の再生2007

    • Author(s)
      青木仁美、原 明、丹羽雅之, ら
    • Organizer
      第111回日本眼科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-04-20
    • Related Report
      2007 Annual Research Report
  • [Book] OCT-3/4 Expressing Cells as Cancer Stem Cells in Human Immature Teratoma : Cancer Differentiation Potential. In : New Cell Differentiation Research Topics2008

    • Author(s)
      Hara A, Oka N, Aoki H, Taguchi A, Yamada Y, Niwa M, Mori H.
    • Publisher
      Nova Science Publisher(New York)
    • Related Report
      2008 Final Research Report
  • [Book] OCT-3/4 Expressing Cells as Cancer stem Cells in Human Immature Teratoma : Cancer Differentiation Potential. In : New Cell Different iation Research Topics.2008

    • Author(s)
      Hara A, Oka N, Aoki H, Taguchi A, Yaiada Y, Niwa M, Mori H.
    • Publisher
      Nova Science Publisher (New York)
    • Related Report
      2008 Annual Research Report
  • [Book] New research on neuronal networks. In: Neuronal Network Research Horizons2007

    • Author(s)
      Hara A, Niwa M, Aoki H, et. al.
    • Publisher
      Nova Science Publish. Inc., NY
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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