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The loss of retinal ganglion cells after administration of aldosterone and development of neuroprotective therapy

Research Project

Project/Area Number 20K09827
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Hirooka Kazuyuki  広島大学, 病院(医), 准教授 (10325350)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords緑内障 / アルドステロン / ミネラロコルチコイド受容体 / 神経保護 / 網膜神経節細胞 / ROCK
Outline of Research at the Start

アルドステロンにより眼圧が上昇することなく網膜神経節細胞死が生じることを我々は発見したが、アルドステロンによる細胞死をどのようにして防ぐかが重要になってくる。グルタミン酸による網膜神経節細胞死とレニン・アンジオテンシン・アルドステロン系により生じる網膜神経節細胞死は別の系であることを我々は明らかにした。アンジオテンシンIIによりRho kinase(ROCK)の発現が上昇することから、網膜における神経細胞死にROCKの関与が考えられる。アルドステロンによって生じる網膜神経節細胞死のメカニズムの一つとしてROCKの役割を明らかにするとともに、ROCKを不活化することによる治療の可能性を探索する。

Outline of Final Research Achievements

Aldosterone was administered systemically in Sprague-Dawley rats. The rats were free access to saline (0.9% NaCl) or water. Eplerenone, mineralocorticoid receptor (MR) antagonist, and hydralazine, vasodilator, were used to determine the effect of antihypertensive drugs on retinal ganglion cell (RGC) loss. Blood pressure was significantly increased in saline intake with or without aldosterone. RGC was significantly decreased in aldosterone treated rats. However, blood pressure did nor affect the RGC loss. Administration of eplerenone or hydralazine in aldosterone treated rat with water instead saline significantly reduced blood pressure. The number of RGC (cells/mm2) was 1868±177 and 1554±34 with eplerenone and hydralazine treated rats, respectively.
The RGC loss observed in experimental aldosterone hypertension rat was blood pressure independent loss. Furthermore, MR antagonist has neuroprotective effects independent of IOP or blood pressure.

Academic Significance and Societal Importance of the Research Achievements

血漿アルドステロン濃度が高いと血圧や眼圧に依存せずに、網膜神経節細胞死をもたらすことが明らかとなった。またこの結果を支持する結果として、血管拡張薬で血圧を下げても網膜神経節細胞死には影響を及ぼさないが、アルドステロンのミネラロコルチコイド受容体に対する作用を抑える薬剤であるミネラロコルチコイド受容体拮抗薬で血圧を下げると網膜神経節細胞死は抑制された。

Report

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

    (6 results)

All 2023 2022

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Blood flow in the optic nerve head in patients with primary aldosteronism2023

    • Author(s)
      Hirooka K, Oki K, Ogawa-Ochiai K, Nakaniida Y, Onoe H, Kiuchi Y
    • Journal Title

      PLos One

      Volume: 18 Issue: 4 Pages: e0285039-e0285039

    • DOI

      10.1371/journal.pone.0285039

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Retinal Renin-Angiotensin-Aldosterone System: Implications for Glaucoma.2022

    • Author(s)
      Hirooka K, Kiuchi Y.
    • Journal Title

      Antioxidants (Basel)

      Volume: 22 Issue: 4 Pages: 610-610

    • DOI

      10.3390/antiox11040610

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aldosterone as a Possible Contributor to Eye Diseases.2022

    • Author(s)
      Tomomi Higashide, Kazuyuki Hirooka, Mitsuhiro Kometani, Kazuhisa Sugiyama
    • Journal Title

      Endocrinology

      Volume: 164(2) Issue: 2 Pages: 1-12

    • DOI

      10.1210/endocr/bqac201

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Compromised Blood Flow in the Optic Nerve Head after Systemic Administration of Aldosterone in Rats: A Possible Rat Model of Retinal Ganglion Cell Loss2022

    • Author(s)
      Yasuyoshi Wada, Tomomi Higashide, Kimikazu Sakaguchi, Atsushi Nagata, Kazuyuki Hirooka, Kazuhisa Sugiyama
    • Journal Title

      Current Eye Research

      Volume: - Issue: 5 Pages: 777-785

    • DOI

      10.1080/02713683.2022.2029907

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Blood flow in the optic nerve head in patients with primary aldosteronism2023

    • Author(s)
      Hirooka K, Oki K, Ogawa-Ochiai K, Onoe H, Kiuchi Y
    • Organizer
      The Association for Research in Vision and Ophthalmology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルドステロンによる網膜神経節細胞死と血圧の関係2023

    • Author(s)
      尾上弘光、廣岡一行、木内良明
    • Organizer
      第127回日本眼科学会総会
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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