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Effect of a multikinase inhibitor on glaucoma surgery model

Research Project

Project/Area Number 17K11496
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionOsaka Medical College

Principal Investigator

Kojima Shota  大阪医科大学, 医学部, 准教授 (10388259)

Co-Investigator(Kenkyū-buntansha) 杉山 哲也  大阪医科大学, 医学部, 非常勤講師 (20298764)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords緑内障 / 濾過手術 / 眼圧 / 瘢痕 / レゴラフェニブ / マルチキナーゼ阻害薬 / 濾過胞 / 線維化
Outline of Final Research Achievements

This study aimed to investigate the effects of regorafenib on intraocular pressure (IOP), bleb formation, and conjunctival changes in experimental glaucoma filtration surgery models. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops or vehicle were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized , In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group. . Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.

Academic Significance and Societal Importance of the Research Achievements

緑内障の治療は眼圧下降が最も効果的であり、代表的な眼圧下降手術である線維柱帯切除術は眼圧下降維持のために結膜濾過胞を形成する必要があり、術後結膜瘢痕癒着抑制を目的として手術時にマイトマイシンC(MMC)などの線維芽細胞増殖抑制薬を用いている。しかし濾過胞感染など重篤な術後副作用が問題となっており、これに代わる薬剤が必要とされている。今回、イヌ緑内障手術モデル眼においてレゴラフェニブ点眼によってMMCと同等の眼圧下降・濾過胞維持効果が示され、より壁が厚く、血管やコラーゲンに富む濾過胞が形成される事が示された。すなわちMMC使用と同等の効果とより安全な結果が得られる可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2020 2019 2018

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

  • [Journal Article] Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison With Mitomycin-C2019

    • Author(s)
      Nemoto E, Kojima S, Sugiyama T, Jin D, Takai S, Maeda M, Kohmoto R, Ueki M, Oku H, Ikeda T.
    • Journal Title

      Int J Mol Sci .

      Volume: 21 Issue: 1 Pages: 63-63

    • DOI

      10.3390/ijms21010063

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 濾過手術モデル眼を用いた結膜組織および線維芽細胞の検討2020

    • Author(s)
      小嶌祥太
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ffects of a multi-kinase inhibitor compared with mitomycin-C on conjunctival scarring in a canine filtration surgery model.2019

    • Author(s)
      Nemoto Emika、Kojima Shota、Sugiyama Tetsuya、Jin Denan、Takai Shinji、Maeda Michiko、Kohmoto Ryohsuke、Ueki Mari、Oku Hidehiro、Ikeda Tsunehiko
    • Organizer
      ARVO Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of a multi-kinase inhibitor compared with mitomycin-C on conjunctival scarring in a canine filtration surgery model.2019

    • Author(s)
      Emika Nemoto, Shota Kojima, Tetsuya Sugiyama, Denan Jin, Shinji Takai, Michiko Maeda, Ryohsuke Kohmoto, Mari Ueki, Hidehiro Oku, Tsunehiko Ikeda
    • Organizer
      ARVO 2019 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] マルチキナーゼ阻害薬点眼のイヌ緑内障濾過手術モデル眼における眼圧および濾過胞形成に対する効果2018

    • Author(s)
      小嶌祥太、杉山哲也、高井真司、金 徳男、前田美智子、根元栄美佳、植木麻里、河本良輔、奥 英弘、池田恒彦
    • Organizer
      第29回日本緑内障学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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