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Analysis of visual central nervous system using ferret glaucoma model

Research Project

Project/Area Number 19K09946
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Fujishiro Takashi  東京大学, 医学部附属病院, 届出研究員 (60789600)

Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords緑内障 / フェレット / 外側膝状体 / 視覚野 / 神経保護 / 中枢神経障害 / グリア細胞 / 視皮質 / 一次視覚野 / Konio細胞 / 外則膝状体 / 視覚中枢
Outline of Research at the Start

ⅰ)免疫組織学的に外側膝状体での神経細胞やグリア系細胞の障害の程度を定量的に評価する。さらに、
ⅱ)外側膝状体の層構造のそれぞれの層の障害差を検討することで、X、Y、W cellの障害の時間的、空間的な障害差を検討する。
ⅲ)視皮質における高眼圧の影響を、神経細胞やグリア系細胞に狙いを絞り組織学的に定量評価を行う。
ⅳ) 解明できたメカニズムをもとに、薬剤による神経保護が外側膝状体、視皮質で有効か検討する

Outline of Final Research Achievements

We have succeeded in creating the ferret glaucoma model by injecting cultured conjunctiva into the anterior chamber of the ferrets for the first time in the world. Using this glaucoma model, we were able to elucidate that the neurological damage caused by glaucoma is not confined to the eyeball alone, but also affects the lateral geniculate nucleus and visual cortex projecting from the glaucoma eye. Axonal damage to retinal ganglion cells and damage to visual center neurons and glial cell activation were confirmed using immunostaining techniques, but no significant association between the degree of intra-ocular pressure elevation and neuronal damage and glial cell activation could be identified. It was also possible to confirm that a decrease in metabolic activity occurred in the visual cortex of the cerebrum projecting from the glaucoma eye.

Academic Significance and Societal Importance of the Research Achievements

今回の我々が行った研究から、緑内障による眼球の神経障害は、眼球だけで発症するのでなく眼球から神経が投射する中枢神経系の外側膝状体、大脳の視覚野にまで障害が及ぶことがわかった。緑内障は高眼圧によって視神経に障害が起き、視野欠損を生じるものとされ、眼圧下降が唯一の治療方法である。しかし、視覚中枢神経系にまで神経障害が起きるということは、眼圧を下げる治療だけでなく視覚中枢神経系の保護が緑内障治療において重要であると確認でき、中枢神経における神経保護を目的とした新しい緑内障治療法の重要性を確認する重要な研究となった。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2022 2020

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

  • [Journal Article] Visual cortex damage in a ferret model of ocular hypertension2022

    • Author(s)
      Fujishiro Takashi、Honjo Megumi、Kawasaki Hiroshi、Aihara Makoto
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 66 Issue: 2 Pages: 205-212

    • DOI

      10.1007/s10384-022-00901-8

    • NAID

      210000172739

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Structural Changes and Astrocyte Response of the Lateral Geniculate Nucleus in a Ferret Model of Ocular Hypertension2020

    • Author(s)
      Fujishiro Takashi、Honjo Megumi、Kawasaki Hiroshi、Asaoka Ryo、Yamagishi Reiko、Aihara Makoto
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 4 Pages: 1339-1339

    • DOI

      10.3390/ijms21041339

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2019-04-18   Modified: 2025-01-30  

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