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Physiological analysis of retinal neuronal modifications induced by D-glutamine accumulation

Research Project

Project/Area Number 20K09838
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionFujita Health University

Principal Investigator

OHKUMA Mahito  藤田医科大学, 医学部, 講師 (50329710)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords網膜細胞 / パッチクランプ / 画像解析 / 網膜 / イオンチャネル / D-アミノ酸 / グルタミン酸測定
Outline of Research at the Start

本研究はD-アミノ酸、特にD-グルタミン蓄積による視覚情報伝達系への影響を調べることを目的とし、この蓄積が確認されている網膜をモデル系として機能解析を行う。実験手法は、マウスおよびイモリ試料での電気生理学的測定(パッチクランプ記録)、およびグルタミン酸可視化法による蛍光測定を主とする。研究期間は4年間とし、この期間内に D-グルタミンの情報伝達系への影響,網膜細胞のどの部分で作用するか,D-アミノ酸の蓄積と除去(代謝)について 解明を試みる。

Outline of Final Research Achievements

I conducted physiological measurements to investigate how information processing in retinal neurons is affected by D-amino acids. In newt retinal neurons, perfusion of D-glutamine reduced the amplitude of voltage-dependent inward currents. Furthermore, small stimuli near the threshold no longer elicited action potentials. Intracellular administration of D-glutamine in retinal third-order neurons significantly increased the amplitude of delayed rectifier outward currents. Additionally, I performed an enzyme-linked fluorescent assay to visualize extracellular glutamate concentrations and confirmed the effects of other substances on retinal information transmission.

Academic Significance and Societal Importance of the Research Achievements

網膜の神経細胞において、Dグルタミンの存在下および細胞内投与により電位依存性電流に変化が見られた結果から、Dアミノ酸の細胞内蓄積による光情報伝達の修飾・抑制が示唆される。また、グルタミン酸の可視化法を応用して、修飾物質による情報伝達物質の放出の動向を直接調べることができた。この結果、妊娠中に性ホルモンにより網膜レベルで視覚情報伝達が修飾される可能性が示唆されたことは学術的のみならず社会的な意義もあると考えている。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Effects of Progesterone and Other Gonadal Hormones on Glutamatergic Circuits in the Retina2023

    • Author(s)
      Ohkuma Mahito、Maruyama Takuma、Ishii Toshiyuki、Igarashi Nozomi、Azuma Keiko、Inoue Tatsuya、Obata Ryo、Miyachi Ei-ichi、Kaneda Makoto
    • Journal Title

      Journal of Nippon Medical School

      Volume: 90 Issue: 4 Pages: 333-345

    • DOI

      10.1272/jnms.JNMS.2023_90-405

    • ISSN
      1345-4676, 1347-3409
    • Year and Date
      2023-08-25
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Iris-derived induced pluripotent stem cells that express GFP in all somatic cells of mice and differentiate into functional retinal neurons2022

    • Author(s)
      Hiramatsu Noriko、Yamamoto Naoki、Ohkuma Mahito、Nagai Noriaki、Miyachi Ei-ichi、Yamatsuta Kumiko、Imaizumi Kazuyoshi
    • Journal Title

      Medical Molecular Morphology

      Volume: 55 Issue: 4 Pages: 292-303

    • DOI

      10.1007/s00795-022-00330-z

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-range axonal projections of transplanted mouse embryonic stem cell-derived hypothalamic neurons into adult mouse brain2022

    • Author(s)
      Kawata Miho、Kodani Yu、Ohkuma Mahito、Miyachi Ei-ichi、Kaneko Yoko S.、Nakashima Akira、Suga Hidetaka、Kameyama Toshiki、Saito Kanako、Nagasaki Hiroshi
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 11 Pages: 1-20

    • DOI

      10.1371/journal.pone.0276694

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A subset of cone bipolar cells expresses the Na+ channel SCN2A in the human retina2021

    • Author(s)
      Kawai Fusao、Ohkuma Mahito、Horiguchi Masayuki、Ichinose Hiroshi、Miyachi Ei-ichi
    • Journal Title

      Experimental Eye Research

      Volume: 202 Pages: 108299-108299

    • DOI

      10.1016/j.exer.2020.108299

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Technique for Retinal Nerve Cell Regeneration with Electrophysiological Functions Using Human Iris-Derived iPS Cells.2021

    • Author(s)
      Yamamoto N, Hiramatsu N, Ohkuma M, Hatsusaka N, Takeda S, Nagai N, Miyachi EI, Kondo M, Imaizumi K, Horiguchi M, Kubo E, Sasaki H.
    • Journal Title

      Cells.

      Volume: 10 (4) Issue: 4 Pages: 743-743

    • DOI

      10.3390/cells10040743

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Enzyme-linked photo-assayによる性ホルモン投与時のマウス網膜グルタミン酸動態の解析2022

    • Author(s)
      大熊真人,金田誠,宮地栄一
    • Organizer
      第69回中部日本生理学会
    • Related Report
      2022 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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