Role of Cdk5/ERK pathway in the pathogenesis of diabetic retinopathy

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K09814
• 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: The University of Tokushima
• Principal Investigator: MITAMURA Yoshinori 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (30287536)
• Co-Investigator(Kenkyū-buntansha): 仙波 賢太郎 徳島大学, 病院, 助教 (10745748) ; 江川 麻理子 徳島大学, 病院, 講師 (70507657)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 外科 / 細胞・組織 / 生体分子 / 糖尿病 / 臨床

Outline of Final Research Achievements

Cyclin-dependent kinase 5 (Cdk5) and extracellular signal-regulated kinase (ERK) are expressed in almost all organs and tissues and are known to play multiple roles, including cell proliferation. However, the activity of Cdk5 and ERK in the eyeball of patients with intraocular proliferative diseases such as proliferative diabetic retinopathy remains unclear. Therefore, we investigated the intraocular concentration of PPARγ and the activity of Cdk5 and ERK using clinical specimen samples obtained during vitreous surgery, and confirmed that the expression of PPARγ and the activation of Cdk5 and ERK were observed in the intraocular fluid (vitreous) and the proliferative membrane formed on the surface of retina in the patients with proliferative diabetic retinopathy. These findings suggest that the Cdk5/ERK signaling pathway may be involved in the pathogenesis of diabetic retinopathy.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

以前は我が国においても糖尿病網膜症が失明原因の第一位を占めていたが、近年の薬物療法や手術治療の目覚ましい進歩により現在は失明原因の第三位となっている。しかし、糖尿病網膜症で著しい視力障害をきたし日常生活や就労に支障をきたす人が後を絶たないのが現実である。今回、我々は硝子体手術時に得られた臨床検体サンプルを用いて、増殖糖尿病網膜症の眼内でPPARγ濃度が上昇しCdk5、ERKが活性化していることを見出し、Cdk5/ERK回路が糖尿病網膜症の病因に関与している可能性が示唆された。このことはCdk5/ERK回路を標的とした糖尿病網膜症の新たな治療法と失明の予防の可能性を示すことができたと考えられる。