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

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Kobe 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
• Keywords: フィブリノーゲン / ICAM-1 / 糖尿病黄斑浮腫 / 糖尿病網膜症

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.

Free Research Field

糖尿病網膜症

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。