The role of the YAP/HIF-1a complex in the pathogenesis of diabetic retinopathy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06787
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kitasato University
• Principal Investigator: Kashihara Toshihide 北里大学, 薬学部, 講師 (20552334)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖尿病網膜症 / YAP / ミュラー細胞

Outline of Final Research Achievements

YAP, a transcriptional coactivator, is essential for cell survival and energy metabolism. In this study, we investigated the activation of YAP and the effect of the interaction between YAP and HIF-1α on the expression level of GLUT1 in the retina of diabetic model rats. We found that YAP in Muller cells is activated in the retinas of streptozotocin-induced diabetic model rats and rats with methylglyoxal intravitreal injection, which is involved in the pathogenesis of diabetes. However, there were no observed changes in the expression levels of HIF-1α and GLUT1 in the retinas of these rats. These results suggest that, while YAP in Muller cells is activated in the diabetic retina, it does not affect the expression of GLUT1.

Free Research Field

眼薬理学

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜症は糖尿病三大合併症の一つであり、本国における成人の失明原因の第2位である。しかしながら、その病態形成に関わる機序は十分に解明されていない。YAPは、細胞の生存やエネルギー代謝を制御する重要な転写共役因子であるが、網膜神経変性疾患における役割は明らかにされていない。本研究は、糖尿病モデルラットのミュラー細胞においてYAPが顕著に活性化することを見出した。このことは、糖尿病網膜症を含む網膜神経変性疾患の病態解明に寄与するものと考えられる。