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Involvement of aquaporin in the formation of optic nerve edema and protective effects of blocking the AQP channels.

Research Project

Project/Area Number 25462763
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionOsaka Medical College

Principal Investigator

Oku Hidehiro  大阪医科大学, 医学部, 准教授 (90177163)

Co-Investigator(Kenkyū-buntansha) Fukuhara Masayuki  大阪医科大学, 医学部, 非常勤講師 (00238510)
Kobayashi Takatoshi  大阪医科大学, 医学部, 講師 (10567093)
Okuno Takashi  大阪医科大学, 医学部, 非常勤講師 (20411366)
Ikeda Tsunehiko  大阪医科大学, 医学部, 教授 (70222891)
Ishizaki Eisuke  大阪医科大学, 医学部, 非常勤講師 (70530434)
Takai Shinji  大阪医科大学, 医学部, 教授 (80288703)
Kida Teruyo  大阪医科大学, 医学部, 講師 (90610105)
Co-Investigator(Renkei-kenkyūsha) Hara Hideaki  岐阜大学, 薬学部, 教授 (20381717)
Research Collaborator Morishita Seita  大阪医科大学, 医学部, 大学院生
Kakurai Keigo  大阪医科大学, 医学部, 大学院生
Horie Taeko  大阪医科大学, 研究補助員
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsaquaporin / グルタミン酸 / 一酸化窒素 / 視神経挫滅 / アストロサイト / aquaporin 4 / TGN-020 / グルタミン / aquaporin-4 / aquaporin-9 / 視神経 / ラット
Outline of Final Research Achievements

Crushing the optic nerve of rats caued 1.8 fold increae of aquaporin 4 (AQP4) expression in the optic nerve. Exposure of optic nerve astrocytes to nitric oxide increased AQP4 expression and enlarged their volume.
Blocking the AQP4 channel by TGN-020 (5.0 mg/kg) caused more decrease of f retinal ganglion cells (RGCs). The ratio of BAX/Bcl-2 also supported the idea that blocking the AQP4 channel was neurodestructive. The glutamate level in the optic nerve was significantly increased after crushing the optic nerve, but TGN-020 depressed the expression of glutamate metabolism-related proteins. Exposure of cultured optic nerve astrocytes to glutamate increased the expression of AQP4 that was also depressed by TGN-020. In addition, glutamate uptake was inhibited by TGN-020. These results indicate that an inhibition of AQP4 enhances neuronal damages after crushing the optic nerve. Inhibition of AQP4 impairs glutamate metabolism which may account for these neurodestructive events.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2016 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 3 results,  Open Access: 2 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] Negative impact of AQP-4 channel inhibition on survival of retinal ganglion cells and glutamate metabolism after crushing optic nerve.2016

    • Author(s)
      Nishikawa Y, Oku H, Morishita S, Horie T, Kida T, Mimura M, Fukumoto M, Kojima S, Ikeda T.
    • Journal Title

      Exp Eye Res

      Volume: 146 Pages: 118-127

    • DOI

      10.1016/j.exer.2015.12.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Nitric Oxide Increases the Expression of Aquaporin-4 Protein in Rat Optic Nerve Astrocytes through the Cyclic Guanosine Monophosphate/Protein Kinase G Pathway.2015

    • Author(s)
      Oku H, Morishita S, Horie T, Kida T, Mimura M, Fukumoto M, Kojima S, Ikeda T.
    • Journal Title

      Ophthalmic Res

      Volume: 54 Issue: 4 Pages: 212-221

    • DOI

      10.1159/000440846

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Systemic simvastatin rescues retinal ganglion cells from optic nerve injury possibly through suppression of astroglial NF-kappaB activation.2014

    • Author(s)
      Morishita S, Oku H, Horie T, Tonari M, Kida T, Okubo A, Sugiyama T, Takai S, Hara H, Ikeda T.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 1 Pages: e84387-e84387

    • DOI

      10.1371/journal.pone.0084387

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in Expression of Aquaporin-4 and Aquaporin-9 in Optic Nerve after Crushing in Rats2014

    • Author(s)
      Hiroyuki Suzuki, Hidehiro Oku, Taeko Horie, Seita Morishita, Masahiro Tonari, Kazuma Oku, Akiko Okubo, Teruyo Kida, Masashi Mimura, Masanori Fukumoto, Shota Kojima, Shinji Takai, Tsunehiko Ikeda
    • Journal Title

      PLoS One

      Volume: 9 Issue: 12 Pages: 1-17

    • DOI

      10.1371/journal.pone.0114694

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Involvement of P2X7 receptors in retinal ganglion cell death after optic nerve crush injury in rats.2013

    • Author(s)
      Kakurai K
    • Journal Title

      Neurosci Lett.

      Volume: 534 Pages: 237-241

    • DOI

      10.1016/j.neulet.2012.11.060

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] P2X(7) receptor activation may be involved in neuronal loss in the retinal ganglion cell layer after acute elevation of intraocular pressure in rats.2013

    • Author(s)
      Sugiyama T, Lee SY, Horie T, Oku H, Takai S, Tanioka H, Kuriki Y, Kojima S, Ikeda T.
    • Journal Title

      Mol Vis.

      Volume: 19 Pages: 2080-2091

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 視神経挫滅モデルにおけるaquaporin 4阻害剤の神経保護作用の検討2015

    • Author(s)
      奥 英弘、森下清太、堀江妙子、三村真士、福本雅格、喜田照代、池田恒彦
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2015-04-16 – 2015-04-19
    • Related Report
      2014 Research-status Report
  • [Presentation] 視神経挫滅モデルにおけるaquaporin 4阻害剤による神経保護作用の検討2015

    • Author(s)
      奥 英弘, 森下 清太, 堀江 妙子, 三村 真士, 福本 雅格, 喜田 照代, 池田 恒彦
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 低酸素負荷による視神経アストロサイトでのAQP4およびAQP9の発現変化と一酸化窒素の関与2014

    • Author(s)
      奥 英弘、森下清太、堀江妙子、大久保安希子、喜田照代、池田恒彦
    • Organizer
      第118回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Research-status Report
  • [Presentation] ラット視神経傷害時のaquaporin 4(AQP4)およびAQP9の発現変化2013

    • Author(s)
      奥 英弘,森下 清太, 戸成 匡宏, 堀江 妙子, 喜田 照代, 池田 恒彦
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Research-status Report
  • [Remarks] 大阪医科大学眼科学教室

    • URL

      http://www.osaka-med.ac.jp/deps/opt/kyousitu.html

    • Related Report
      2014 Research-status Report
  • [Remarks] 大阪医科大学眼科学教室

    • URL

      http://www.osaka-med.ac.jp/deps/opt/

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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