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Research for the pathophysiological investigation of diabetic macular edema focusing on fibrinogen accumulation in the retina.

Research Project

Project/Area Number 21K09719
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Imai Hisanori  神戸大学, 医学部附属病院, 講師 (90569211)

Co-Investigator(Kenkyū-buntansha) 三木 明子  神戸大学, 医学部附属病院, 助教 (10726988)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2023: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsフィブリノーゲン / ICAM-1 / 糖尿病黄斑浮腫 / 糖尿病網膜症 / 網膜血管内皮細胞 / Müller細胞 / 細胞間接着分子1 / 網膜神経節細胞
Outline of Research at the Start

多くの糖尿病黄斑浮腫(DME)は、既知の病態に対する集学的治療にて治療可能となった。しかし、いずれにも抵抗する難治DMEは存在する。本研究では、難治DMEをターゲットに、DME内に滲出する血漿成分の病態への関与について検討し、これまで未知であったDMEの病態を解明する。特にDME内に析出するフィブリノーゲンが神経、血管、そしてグリアといった各網膜細胞に及ぼす影響を中心課題として検討する。

Outline of Final Research Achievements

The purpose of this study was to investigate the involvement of fibrinogen (Fb) in the pathophysiology of diabetic macular edema. We administered high concentrations of Fb into the vitreous cavity of normal mice and evaluated its impact on retinal function. The results of Western blot and immunostaining showed that the expression of the glial cell marker (GFAP) was significantly upregulated, while the expression of the ganglion cell marker (TUBB3) was significantly downregulated. Furthermore, electroretinography indicated that the amplitude of each waveform decreased, suggesting a decline in retinal function. These changes were neutralized by the administration of an anti-ICAM-1 antibody. These findings suggest that high concentrations of Fb are injurious to the retina and that this effect may be modulated by Fb/ICAM-1 intracellular signaling.

Academic Significance and Societal Importance of the Research Achievements

現在、糖尿病黄斑浮腫(DME)は既知の病態に対する各種治療を駆使した集学的治療によってある程度治療できるようになった。しかし、一定の割合で難治例が存在する。この結果は、未知の病態の存在を示唆する。本研究の目的は、浮腫内に滲出するフィブリノーゲン(Fb)と未知の病態との関連を解明することであった。これまで眼内Fb濃度に着目して病態解明を進める研究は国内外を通じて未だなく、独自性が高い。本研究結果は、DMEの発症・進展機序に新たな知見を与え、創薬の観点からも、学術的・臨床的に意義が大きい。

Report

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

    (19 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (11 results) (of which Invited: 3 results)

  • [Journal Article] Short-Term Outcomes of Intravitreal Faricimab Injection for Diabetic Macular Edema2023

    • Author(s)
      Kusuhara Sentaro、Kishimoto-Kishi Maya、Matsumiya Wataru、Miki Akiko、Imai Hisanori、Nakamura Makoto
    • Journal Title

      Medicina

      Volume: 59 Issue: 4 Pages: 665-665

    • DOI

      10.3390/medicina59040665

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Removal of Sub-Internal Limiting Membrane Hemorrhage Secondary to Retinal Arterial Macroaneurysm Rupture: Internal Limiting Membrane Non-Peeling Technique2023

    • Author(s)
      Kimura Akari、Imai Hisanori、Iwane Yukako、Kishimoto Maya、Sotani Yasuyuki、Yamada Hiroko、Matsumiya Wataru、Miki Akiko、Kusuhara Sentaro、Nakamura Makoto
    • Journal Title

      Journal of Clinical Medicine

      Volume: 12 Issue: 9 Pages: 3291-3291

    • DOI

      10.3390/jcm12093291

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 継続通院困難な糖尿病黄斑症患者に対して硝子体手術と黄斑部への外科的介入が奏効した1例2023

    • Author(s)
      岩根友佳子、今井尚徳、曽谷育之、山田裕子、大石麻利子、中村誠
    • Journal Title

      あたらしい眼科

      Volume: 40 Pages: 95-100

    • Related Report
      2022 Research-status Report
  • [Journal Article] Removal of Subfoveal Massive Hard Exudates through an Intentional Macular Hole in Patients with Diabetic Maculopathy: A Report of Three Cases2022

    • Author(s)
      Iwane Yukako、Imai Hisanori、Yamada Hiroko、Sotani Yasuyuki、Oishi Mariko、Nakamura Makoto
    • Journal Title

      Case Reports in Ophthalmology

      Volume: 13 Issue: 2 Pages: 649-656

    • DOI

      10.1159/000526150

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased expression of Protein S in eyes with diabetic retinopathy and diabetic macular edema.2021

    • Author(s)
      Sugimoto M, Kondo M, Yasuma T, D'Alessandro-Gabazza CN, Toda M, Imai H, Nakamura M, Gabazza EC.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 10449-10449

    • DOI

      10.1038/s41598-021-89870-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin-like growth factor-2 regulates basal retinal insulin receptor activity2021

    • Author(s)
      Zolov Sergey N.、Imai Hisanori、Losiewicz Mandy K.、Singh Ravi S.J.、Fort Patrice E.、Gardner Thomas W.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100712-100712

    • DOI

      10.1016/j.jbc.2021.100712

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to branch retinal vein occlusion2021

    • Author(s)
      Yamada Hiroko、Imai Hisanori、Tetsumoto Akira、Hayashida Mayuka、Otsuka Keiko、Miki Akiko、Kusuhara Sentaro、Nakamura Makoto
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 8460-8460

    • DOI

      10.1038/s41598-021-88149-z

    • NAID

      120007038635

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The long-term effect of cystotomy with fibrinogen clot removal for a cystoid macular edema secondary to idiopathic macular telangiectasia type 12021

    • Author(s)
      Maki Hitomi、Imai Hisanori、Yamada Hiroko、Tetsumoto Akira、Hayashida Mayuka、Otsuka Keiko、Miki Akiko、Nakamura Makoto
    • Journal Title

      RETINAL Cases & Brief Reports

      Volume: Publish Ahead of Print Issue: 2 Pages: 101-104

    • DOI

      10.1097/icb.0000000000001117

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 糖尿病黄斑浮腫アップデート- 明日からできる治療の使い分け-2023

    • Author(s)
      今井尚徳
    • Organizer
      第77回日本臨床眼科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 糖尿病眼合併症に対する外科的治療の Pitfalls 安全、確実な手術のための注意点2023

    • Author(s)
      今井尚徳
    • Organizer
      第29回日本糖尿病眼学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 難治性糖尿病黄斑浮腫に対する嚢胞様腔内壁切開術の長期経過の検討2023

    • Author(s)
      山田裕子、今井尚徳、曽谷育之 、岸真椰、平野真由香、大塚慶子、 三木明子 、中村誠
    • Organizer
      第29回日本糖尿病眼学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 糖尿病網膜症診療の現在2023

    • Author(s)
      今井尚徳
    • Organizer
      第38回日本糖尿病合併症学会・第29回日本糖尿病眼学会総会合同シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] 画像診断を利用した増殖糖尿病網膜症に対する硝子体手術2022

    • Author(s)
      今井尚徳
    • Organizer
      第61回日本網膜硝子体学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 抗VEGF治療に抵抗するDMEに対する嚢胞様腔内壁切開術・フィブリノーゲン塊摘出2022

    • Author(s)
      今井尚徳
    • Organizer
      第76回日本臨床眼科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] The effect of cystotomy for treatment refractory diabetic macular edema2022

    • Author(s)
      Hisanori Imai
    • Organizer
      FUJIRETINA
    • Related Report
      2022 Research-status Report
  • [Presentation] 網膜血管病に続発する嚢胞様黄斑浮腫と組織内フィブリノーゲンの関連2022

    • Author(s)
      今井尚徳
    • Organizer
      第128回京都眼科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 難治嚢胞様黄斑浮腫に対する嚢胞様腔内壁切開の長期成績2021

    • Author(s)
      今井尚徳
    • Organizer
      第44回日本眼科手術学会学術総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] The effect of cystotomy for treatment refractory diabetic macular edema2021

    • Author(s)
      Hisanori Imai
    • Organizer
      第125回日本眼科学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 難治糖尿病黄斑浮腫に対する外科治療2021

    • Author(s)
      今井尚徳
    • Organizer
      第75回日本臨床眼科学会
    • Related Report
      2021 Research-status Report
    • Invited

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

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