Elucidation of the Pathogenesis of Diabetic Retinopathy Focusing on Cellular Senescence Induced by Oxidative Stress and the STING Pathway

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16866
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Tohoku University
• Principal Investigator: Yasuda Masayuki 東北大学, 大学病院, 助教 (00569585)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 糖尿病網膜症 / 酸化ストレス / 炎症

Outline of Final Research Achievements

Diabetic retinopathy is a multifactorial disease, and oxidative stress has been recognized as one of its pathogenic factors. In this study, we measured the oxidative stress level (dROM) and antioxidant capacity (BAP) as markers of blood oxidative stress and investigated their association with diabetic retinopathy. As a result, dROM levels were elevated in patients with diabetes and proliferative diabetic retinopathy. In experiments using Muller cells, high glucose culture significantly increased the gene expression of STING, which is known to be induced by oxidative stress. Furthermore, the addition of a STING inhibitor suppressed the gene expression of MCP-1, an inflammatory cytokine. These findings suggest the involvement of the STING pathway in the pathogenesis of diabetic retinopathy.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜症は、慢性血糖による細小血管合併症の一つであるが、同程度に血糖降下しても予後には個人差があり、新たな治療法の開発が必要である。糖尿病網膜症は多因子疾患であり、酸化ストレスや炎症が重要な役割を果たすとされている。本研究で着目したSTINGは酸化ストレスによるDNA障害により活性化し、炎症性サイトカイン産生を誘導することが知られている。本研究の成果は、糖尿病網膜症の病態としてSTING経路の関与を示唆し、将来的にSTING阻害剤という新たな糖尿病網膜症の治療薬の開発研究に貢献することが期待される。