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Involvement of oxidative stress in the pathophysiology of retinitis pigmentosa

Research Project

Project/Area Number 19K18900
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionSaga University (2020-2021)
Fukuoka Dental College (2019)

Principal Investigator

YOSHIDA NORIKO  佐賀大学, 医学部, 特任教授 (70725853)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords酸化ストレス / 網膜色素変性
Outline of Research at the Start

網膜色素変性(Retinitis Pigmentosa: RP)は、様々な遺伝子異常によって視細胞が障害される疾患群で未だ有効な治療法がない。我々は、網膜への酸化ストレスが、視細胞死の誘導や慢性炎症への関与等、RPの病態に広く関与することを報告してきた。本研究では、RP患者の臨床サンプルを用いて酸化ストレスマーカーを同定し、臨床所見との相関性を検討することにより、RPの病態を反映する客観的な評価指標(バイオマーカー)としての可能性について検証する。これらにより、病態の分析・解明、疾患の予後予測及び新たな治療戦略に繋がるような成果を目指す。

Outline of Final Research Achievements

The antioxidant/oxidant markers were analyzed in the serum, aqueous humor and vitreous samples from the RP patients and the healthy controls. The serum superoxide dismutase 3 (SOD3) activity in the severe degeneration group with macular involvement was significantly lower compared with those in the mild degeneration group. In addition, we assessed the levels of peripheral blood monocytes to evaluate their correlation with clinical findings. The CD14++CD16+ intermediate monocytes was significantly increased in RP patients, which was correlated with the rate of decline of retinal sensitivity in the macular area. These results suggest that the serum SOD3 activity may be related to disease severity, and that activation of peripheral blood monocytes is important for cone cell death in RP.

Academic Significance and Societal Importance of the Research Achievements

網膜色素変性(RP)は、様々な遺伝子異常によって視細胞が障害される疾患群で未だ有効な治療法がない。我々は、ゲノムの酸化損傷によるミクログリアの活性化を介した慢性炎症への関与や視細胞死の誘導など、網膜への酸化ストレスがRPの病態に広く関与することを報告してきた。本研究では、RP患者の臨床サンプルを用いて酸化ストレスマーカーを解析し、血清SOD3活性がRPの病態を反映するバイオマーカーであることの可能性について検証した。また、末梢血中の単球を解析して末梢血中のintermediate monocytesの増加とRPにおける錐体細胞死への関与を明らかにし、新たな治療標的として同定した。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2020

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

  • [Journal Article] Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa2022

    • Author(s)
      Funatsu Jun, Murakami Yusuke, Shimokawa Shotaro, Nakatake Shunji, Fujiwara Kohta, Okita Ayako, Fukushima Masatoshi, Shibata Kensuke, Yoshida Noriko, et al.
    • Journal Title

      PNAS Nexus

      Volume: 1 Issue: 1

    • DOI

      10.1093/pnasnexus/pgac003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term Outcomes of Cataract Surgery in Patients with Retinitis Pigmentosa2022

    • Author(s)
      Shun Nakamura, Kohta Fujiwara, Noriko Yoshida, Yusuke Murakami, Shotaro Shimokawa, Yoshito Koyanagi, Yasuhiro Ikeda, Koh-Hei Sonoda
    • Journal Title

      Ophthalmol retina

      Volume: 4 Issue: 4 Pages: 268-272

    • DOI

      10.1016/j.oret.2021.12.010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aqueous Flare and Progression of Visual Field Loss in Patients With Retinitis Pigmentosa.2020

    • Author(s)
      Fujiwara K, Ikeda Y, Murakami Y, Tachibana T, Funatsu J, Koyanagi Y, Nakatake S, Shimokawa S, Yoshida N, Nakao S, Hisatomi T, Ishibashi T, Sonoda KH.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 26 Issue: 8 Pages: 26-26

    • DOI

      10.1167/iovs.61.8.26

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of Topical Dorzolamide on Cystoid Macular Edema in Retinitis Pigmentosa2020

    • Author(s)
      Shimokawa Shotaro、Fujiwara Kohta、Murakami Yusuke、Funatsu Jun、Nakatake Shunji、Yoshida Noriko、Sonoda Koh-Hei、Ikeda Yasuhiro
    • Journal Title

      Ophthalmology Retina

      Volume: 4 Issue: 10 Pages: 1036-1039

    • DOI

      10.1016/j.oret.2020.05.012

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Recurrence Rate of Cystoid Macular Edema with Topical Dorzolamide Treeatment and Risk Factors in Retinitis Pigmentosa2021

    • Author(s)
      Shimokawa S, Murakami Y, Fujiwara K, Funatsu J, Nakatake S, Koyanagi Y, Akiyama M, Yoshida N, Takeda A, Ikeda Y, Sonoda KH
    • Organizer
      ARVO, San Francisco, USA
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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