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Analysis of the role of MCP-1/CCR2 in the wound healing process after glaucoma surgery

Research Project

Project/Area Number 21K16899
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Kojima Sachi  熊本大学, 病院, 講師 (80632661)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords緑内障 / 緑内障濾過手術 / 創傷治癒 / MCP-1 / 生体眼イメージング
Outline of Research at the Start

緑内障濾過手術は眼圧下降に優れた手術であるが、創部に生じる過剰な線維化により濾過胞機能不全となる予後不良症例も存在する。我々は、房水内のMCP(monocyte chemoattractant protein)-1濃度上昇が手術予後のリスクファクターであり、手術で作成した房水流出路の閉塞過程に強く影響していることまで明らかにしているが、MCP-1が関わる線維化進展の分子メカニズムについての知見は乏しい。本研究では緑内障濾過手術後の線維化におけるMCP-1とその受容体であるCCR2の役割を分子細胞生物学的に検証し、治療成績向上につながる線維化抑制の新しい理解を見出すことを目的とする。

Outline of Final Research Achievements

Intravital imaging confirmed that MCP-1 loading, a risk factor for glaucoma filtration surgery, activates inflammatory cells (LysM-positive cells) in the subconjunctival tissue. A ROCK inhibitor inhibited the activation of these cells. Single-cell RNA sequencing was performed to analyze the lineage of cells with migratory activity following MCP-1 loading, revealing that there was no difference in the cell population between the control and MCP-1 loading, and that macrophages and fibroblasts were predominant in the surgical model. Furthermore, macrophages were predominant among LysM-positive cells observed by intravital imaging. These results suggest that macrophages may be involved in conjunctival wounds, and that MCP-1 may be involved in macrophage activation, which may be inhibited by a ROCK inhibitor.

Academic Significance and Societal Importance of the Research Achievements

緑内障は日本において中途失明の第一位となっている進行性の視神経症であり、現在のところ眼圧下降のみが唯一エビデンスのある治療法である。薬物療法やレーザー治療で十分な効果が得られない場合は手術療法を行う。緑内障濾過手術は眼圧下降効果に優れた手術であるが、術創に働く創傷治癒に術後成績に大きく関わる。房水内MCP-1は緑内障濾過手術のリスクファクターである。本研究成果による、濾過手術後の創傷治癒過程におけるMCP-1の役割や、その抑制過程を明らかにすることは、緑内障濾過手術後の創傷治癒機序解明の一助となり、最終的には緑内障による失明を減らすことに寄与することが期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (18 results)

All 2024 2023 2022 2021

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Factors associated with visual field or structure progression occurring first in a prospective study on patients with untreated open-angle glaucoma with normal intraocular pressure2023

    • Author(s)
      Sakata Rei、Araie Makoto、Yoshitomi Takeshi、et al
    • Journal Title

      Eye

      Volume: 38 Issue: 4 Pages: 737-744

    • DOI

      10.1038/s41433-023-02766-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trabeculotomy Using the Kahook Dual Blade for Exfoliation Glaucoma and Primary Open Angle Glaucoma: Comparison of Outcomes According to Incision Range2023

    • Author(s)
      Irie Anna、Nakashima Kei-Ichi、Inoue Toshihiro、Kojima Sachi、Takihara Yuji、Takahashi Eri
    • Journal Title

      Journal of Glaucoma

      Volume: 33 Issue: 4 Pages: 270-276

    • DOI

      10.1097/ijg.0000000000002323

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk factors for Baerveldt glaucoma drainage implantation for uveitic glaucoma2023

    • Author(s)
      Manako Kiyofumi、Takahashi Eri、Saruwatari Junji、Matsumura Tomoyo、Kojima Sachi、Inoue Toshihiro
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 4473-4473

    • DOI

      10.1038/s41598-023-29244-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factors associated with the surgical outcomes of Baerveldt glaucoma implant for open-angle glaucoma, an age-related eye disease2022

    • Author(s)
      Iraha Satoshi、Takihara Yuji、Urahashi Yui、Watanabe Takahiro、Nakamura Kenichi、Urahashi Mai、Watanabe-Kitamura Fumika、Nakashima Kei-Ichi、Takahashi Eri、Kojima Sachi、Tanihara Hidenobu、Inoue Toshihiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1359-1359

    • DOI

      10.1038/s41598-021-04570-4

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparing Surgical Outcomes in Neovascular Glaucoma between Tube and?Trabeculectomy2022

    • Author(s)
      Iwasaki Kentaro、Kojima Sachi、Wajima Ryotaro、Okazaki Tomoyuki、Yokoyama Yu、Inoue Toshihiro、Higashide Tomomi、Miki Atsuya、Nakazawa Toru、Inatani Masaru
    • Journal Title

      Ophthalmology Glaucoma

      Volume: 5 Issue: 6 Pages: 672-680

    • DOI

      10.1016/j.ogla.2022.05.003

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated soluble vascular endothelial growth factor receptor levels in aqueous humor from patients with different types of glaucoma.2022

    • Author(s)
      Kenichi Nakamura, Sachi Kojima, Miyuki Inoue-Mochita, Hidenobu Tanihara, Toshihiro Inoue
    • Journal Title

      Experimental Eye Research

      Volume: 223 Pages: 109204-109204

    • DOI

      10.1016/j.exer.2022.109204

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Outcomes and risk factors for ab interno trabeculotomy with a Kahook Dual Blade2022

    • Author(s)
      Murata Natsumi、Takahashi Eri、Saruwatari Junji、Kojima Sachi、Inoue Toshihiro
    • Journal Title

      Graefe's Archive for Clinical and Experimental Ophthalmology

      Volume: 261 Issue: 2 Pages: 503-511

    • DOI

      10.1007/s00417-022-05799-z

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The occurrence of optic disc haemorrhage in primary open-angle glaucoma eyes with lower normal pressure and its relating factors.2021

    • Author(s)
      Sakata R, Yoshitomi T, Araie M; for Lower Normal Pressure Glaucoma Study Members in Japan Glaucoma Society.
    • Journal Title

      Acta Ophthalmol.

      Volume: 99 Issue: 1

    • DOI

      10.1111/aos.14506

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 濾過手術アップデート2024

    • Author(s)
      小島祥
    • Organizer
      第128回日本眼科学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Treatment outcomes of Baerveldt glaucoma implantation in patients with neovascular glaucoma with versus without a history of trabeculectomy2023

    • Author(s)
      Sachi Kojima, Kenichi Nakamura, Yuji Takihara, Toshihiro Inoue
    • Organizer
      10th World Glaucoma Congress
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 毛様溝挿入した緑内障インプラントのチューブ内に硝子体嵌頓をきたした落屑緑内障2023

    • Author(s)
      諸岡研人、小島祥、井上俊洋
    • Organizer
      第39回九州緑内障カンファレンス
    • Related Report
      2023 Annual Research Report
  • [Presentation] 隅角検査を極める2023

    • Author(s)
      小島祥
    • Organizer
      第34回緑内障学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 前眼部OCTによる緑内障術後評価2022

    • Author(s)
      小島祥
    • Organizer
      第126回日本眼科学会
    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Invited
  • [Presentation] 血管新生緑内障に対するバルベルト緑内障インプラント2022

    • Author(s)
      中村健一、小島祥、瀧原祐史、井上俊洋
    • Organizer
      第33回日本緑内障学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 同一薬剤カテゴリーにおけるブリモニジン酒石酸塩・ブリンゾラミド配合懸濁性点眼液切り替え成績2022

    • Author(s)
      小島摂、小島祥、佐藤一徳、浦橋舞衣、瀧原祐史、中島圭一、高橋枝里、井上俊洋
    • Organizer
      第38回九州緑内障カンファレンス
    • Related Report
      2022 Research-status Report
  • [Presentation] 緑内障レーザー治療のトピックス2021

    • Author(s)
      小島祥
    • Organizer
      第125回日本眼科学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 同一薬剤カテゴリーにおけるブリモニジン酒石酸塩・ブリンゾラミド配合懸濁性点眼液切り替え成績2021

    • Author(s)
      幸野理久、小島祥、佐藤一徳、浦橋舞衣、瀧原祐史、中島圭一、高橋枝里、井上俊洋
    • Organizer
      第37回九州緑内障カンファレンス
    • Related Report
      2021 Research-status Report
  • [Presentation] 当院におけるパターンスキャンレーザー線維柱帯形成術の治療成績2021

    • Author(s)
      佐藤一徳、小島祥、小田原敦子、瀧原祐史、中島圭一、渡邊隆弘、浦橋舞衣、小島摂、高橋枝里、井上俊洋
    • Organizer
      第31回緑内障学会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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