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Development of a novel treatment for anti-VEGF resistant diabetic macular edema using ROCK inhibitor

Research Project

Project/Area Number 19K18846
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Arima Mitsuru  九州大学, 大学病院, 学術研究員 (60772845)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords糖尿病黄斑浮腫 / 抗VEGF治療 / ROCK / 分子標的治療
Outline of Research at the Start

糖尿病網膜症は本邦における主要な成人失明原因疾患であるが、視機能障害の主因は黄斑浮腫である。現在、黄斑浮腫に対して最も有効な治療法は抗血管内皮増殖因子抗体の硝子体注射(抗VEGF治療)であるが、約4割の患者では治療効果がない。我々はこれまでの研究により、抗VEGF治療抵抗性黄斑浮腫の形成にROCKが関与することを明らかにした。本研究では新規分子標的治療薬(抗ROCK治療)の創製を目指し、ROCKの具体的作用機序の特定を行う。

Outline of Final Research Achievements

The first treatment modality for diabetic macular edema (DME) is intravitreal injection of anti-vascular endothelial growth factor agents (anti-VEGF treatment), but about 40% of patients are resistant to anti-VEGF treatment (rDME). We have already identified the involvement of ROCK in the pathogenesis of rDME by analyzing vitreous samples from rDME patients and retinal samples from rDME animal models. In this study, we demonstrated that ROCK (especially ROCK2) is involved in rDME formation through the BRB disruption by inflammatory cytokines.

Academic Significance and Societal Importance of the Research Achievements

本邦におけるDME患者数は約60万人に上ると推定されている。抗VEGF治療抵抗DMEに対しては現在打つ手がなく、視機能低下を抑止する術がない。本研究で我々は、ROCKがrDME治療標的分子となることを示した。海外との共同研究により、ROCK阻害剤のrDMEへの治療効果も確認している。DMEは壮年期にも発症する疾患であるため、臨床応用できれば多数の患者の社会復帰に貢献することができる。

Report

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

    (6 results)

All 2020 Other

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

  • [Int'l Joint Research] Queen's University(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Queen's University(英国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Shahid Beheshti University(イラン)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Optical Coherence Tomography Angiography of Choroidal Neovascularization in Immune Choroiditis Following Acute Retinal Necrosis2020

    • Author(s)
      Nakamura S, Nakao S, Shiose S, Kohno RI, Hasegawa E,Sonoda KH
    • Journal Title

      Eur J Ophthalmol

      Volume: - Issue: 1 Pages: 4185-4185

    • DOI

      10.1038/s41598-021-83334-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Claudin-5 Redistribution Induced by Inflammation Leads to Anti-VEGF-Resistant Diabetic Macular Edema.2020

    • Author(s)
      Arima M, Nakao S, Yamaguchi M, Feng H, Fujii Y, Shibata K, Wada I, Kaizu Y, Ahmadieh H, Ishibashi T, Stitt AW, Sonoda KH.
    • Journal Title

      Diabetes

      Volume: 69 Issue: 5 Pages: 981-999

    • DOI

      10.2337/db19-1121

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Claudin-5 Redistribution Induced by Inflammation Leads to Anti-VEGF Resistant Diabetic Macular Edema2020

    • Author(s)
      有馬 充
    • Organizer
      第26回日本糖尿病眼学会総会
    • Related Report
      2020 Annual Research Report
    • Invited

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Published: 2019-04-18   Modified: 2022-01-27  

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