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ROCK inhibitor for treating intraocular fibrosis by modulating epithelial-to-mesenchymal transition.

Research Project

Project/Area Number 20K09828
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Ishikawa Keijiro  九州大学, 医学研究院, 助教 (00795304)

Co-Investigator(Kenkyū-buntansha) 松永 直哉 (門田直哉)  九州大学, 薬学研究院, 教授 (10432915)
武田 篤信  九州大学, 医学研究院, 准教授 (40560313)
中尾 新太郎  独立行政法人国立病院機構九州医療センター(臨床研究センター), その他部局等, 客員研究員 (50583027)
村上 祐介  九州大学, 大学病院, 講師 (50634995)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords網膜症 / 糖尿病網膜症 / 網膜剥離 / 形質転換 / リポソーム / 増殖性硝子体網膜症 / 線維化 / 網膜 / 細胞増殖 / 増殖硝子体網膜症 / 細胞移植
Outline of Research at the Start

加齢黄斑変性、糖尿病網膜症、増殖硝子体網膜症の診療で、抗VEGF療法や手術治療に抵抗性で視機能が温存できない症例が存在するが、治療抵抗例の主病態である眼内線維増殖に対しては有効な治療薬がない。これまで増殖性網膜硝子体疾患に伴う線維組織の網羅的な遺伝子発現解析を基盤とした病態解明研究に取り組み、細胞の形質転換が眼内線維増殖に必須のプロセスであり、ROCK阻害薬が効率的に形質転換を抑制する薬剤として有望であることを明らかにしている。本研究で、増殖性網膜硝子体疾患に対するROCK阻害薬の臨床応用に向けて、頻回投与を回避するためのドラッグデリバリーの開発と、細胞移植治療補助薬としての可能性を検討する。

Outline of Final Research Achievements

In this study, the pharmacodynamic properties of liposome-encapsulated ROCK inhibitors were investigated in different animal models. The liposome encapsulation showed significantly improved retention in the eye compared to the non-liposome drug. In addition, in the study of the inhibitory effect on intraocular fibroproliferation, the liposome-encapsulated ROCK inhibitor was found to be effective for a long period of time with fewer intraocular administrations. In addition, the intraocular expression of periostin, a biomarker that reflects intraocular fibrosis, was also significantly suppressed by the liposomal formulation.

Academic Significance and Societal Importance of the Research Achievements

眼内線維増殖に対する薬剤は、未だ臨床応用されておらず新規治療薬開発が望まれている。今回の研究成果により、眼内線維増殖抑制が期待されるROCK阻害薬の臨床応用に向けて、リポソーム化修飾することで、頻回の眼内注射を避けることができる可能性が示された。

Report

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

    (12 results)

All 2023 2022 2021 2020

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Drainage Retinotomy Confers Risk of Epiretinal Membrane Formation After Vitrectomy for Rhegmatogenous Retinal Detachment Repair2022

    • Author(s)
      Ishikawa Keijiro、Akiyama Masato、Mori Kenichiro、Nakama Takahito、Notomi Shoji、Nakao Shintaro、Kohno Ri-ichiro、Takeda Atsunobu、Sonoda Koh-Hei
    • Journal Title

      American Journal of Ophthalmology

      Volume: 234 Pages: 20-27

    • DOI

      10.1016/j.ajo.2021.07.028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] <i>TNFRSF10A</i> downregulation induces retinal pigment epithelium degeneration during the pathogenesis of age-related macular degeneration and central serous chorioretinopathy2022

    • Author(s)
      Mori Kenichiro、Ishikawa Keijiro、Fukuda Yosuke、Ji Rui、Wada Iori、Kubo Yuki、Akiyama Masato、Notomi Shoji、Murakami Yusuke、Nakao Shintaro、Arakawa Satoshi、Shiose Satomi、Hisatomi Toshio、Yoshida Shigeo、Kannan Ram、Sonoda Koh-Hei
    • Journal Title

      Human Molecular Genetics

      Volume: - Issue: 13 Pages: 2194-2206

    • DOI

      10.1093/hmg/ddac020

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Surgical Outcomes of Contrast Sensitivity and Visual Acuity in Uveitis-Associated Cataract2021

    • Author(s)
      Takeda Atsunobu、Hasegawa Eiichi、Notomi Shoji、Ishikawa Keijiro、Arima Mitsuru、Murakami Yusuke、Nakao Shintaro、Hisatomi Toshio、Sonoda Koh-Hei
    • Journal Title

      Clinical Ophthalmology

      Volume: 15 Pages: 2665-2673

    • DOI

      10.2147/opth.s314173

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Volumetric Three-Dimensional Optical Coherence Tomography Angiography of Retinal Neovascularization in Proliferative Diabetic Retinopathy2021

    • Author(s)
      Nakao Shintaro、Kaizu Yoshihiro、Horie Juun、Wada Iori、Arima Mitsuru、Fukuda Yosuke、Ishikawa Keijiro、Sonoda Koh-Hei
    • Journal Title

      RETINAL Cases &amp; Brief Reports

      Volume: - Issue: 3 Pages: 315-320

    • DOI

      10.1097/icb.0000000000001183

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Drusen and pigment abnormality predict the development of neovascular age-related macular degeneration in Japanese patients2021

    • Author(s)
      Notomi Shoji、Shiose Satomi、Ishikawa Keijiro、Fukuda Yosuke、Kano Kumiko、Mori Kenichiro、Wada Iori、Kaizu Yoshihiro、Matsumoto Hidetaka、Akiyama Masato、Sonoda Koh-Hei
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 7 Pages: e0255213-e0255213

    • DOI

      10.1371/journal.pone.0255213

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changes in metamorphopsia after the treat-and-extend regimen of anti-VEGF therapy for macular edema associated with branch retinal vein occlusion2020

    • Author(s)
      Mori Kenichiro、Ishikawa Keijiro、Wada Iori、Kubo Yuki、Kobayashi Yoshiyuki、Nakama Takahito、Haruta Masatoshi、Akiyama Masato、Nakao Shintaro、Yoshida Shigeo、Sonoda Koh-Hei
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 10 Pages: e0241343-e0241343

    • DOI

      10.1371/journal.pone.0241343

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitreous levels of interleukin-35 as a prognostic factor in B-cell vitreoretinal lymphoma2020

    • Author(s)
      Takeda Atsunobu、Hasegawa Eiichi、Nakao Shintaro、Ishikawa Keijiro、Murakami Yusuke、Hisatomi Toshio、Arima Mitsuru、Yawata Nobuyo、Oda Yoshinao、Kimura Kazuhiro、Yoshikawa Hiroshi、Sonoda Koh-Hei
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 15715-15715

    • DOI

      10.1038/s41598-020-72962-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Periostin and tenascin-C interaction promotes angiogenesis in ischemic proliferative retinopathy2020

    • Author(s)
      Kubo Yuki、Ishikawa Keijiro、Mori Kenichiro、Kobayashi Yoshiyuki、Nakama Takahito、Arima Mitsuru、Nakao Shintaro、Hisatomi Toshio、Haruta Masatoshi、Sonoda Koh-Hei、Yoshida Shigeo
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 9299-9299

    • DOI

      10.1038/s41598-020-66278-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitrectomy with peripapillary internal limiting membrane peeling for macular retinoschisis associated with normal-tension glaucoma2020

    • Author(s)
      Ishikawa Keijiro、Fukui Takuma、Nakao Shintaro、Shiose Satomi、Sonoda Koh-Hei
    • Journal Title

      American Journal of Ophthalmology Case Reports

      Volume: 18 Pages: 100663-100663

    • DOI

      10.1016/j.ajoc.2020.100663

    • Related Report
      2020 Research-status Report
  • [Presentation] 増殖糖尿病網膜症に対する硝子体手術後の線維増殖に対する治療法開発2023

    • Author(s)
      石川桂二郎
    • Organizer
      第127回日本眼科学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Effects of Liposome-encapsulated Ripasudil on Proliferative Vitreoretinopathy2021

    • Author(s)
      Rui ji, Ishikawa K, Mori K, Naoya Matsunaga, Wada I, Nakama T, Nakao S, Shigehiro Ohdo, Sonoda KH;
    • Organizer
      The 14th Joint Meeting of Japan-China-Korea Ophthalmologists, Fukuoka,Japan,
    • Related Report
      2021 Research-status Report
  • [Presentation] Effects of Liposome-encapsulated Ripasudil on Proliferative Vitreoretinopathy2021

    • Author(s)
      Rui Ji1, Keijiro Ishikawa1, Kenichiro Mori1, Naoya Matsunaga2, Iori Wada1, Takahito Nakama1, Shintaro Nakao1, Shigehiro Ohdo2, Koh-Hei Sonoda1
    • Organizer
      第125回 日本眼科学会総会
    • Related Report
      2020 Research-status Report

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

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