Study of cytokine-dependent epigenetic regulation mechanism in refractory ischemic retinal disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09768
• 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: University of Fukui
• Principal Investigator: Takamura Yoshihiro 福井大学, 学術研究院医学系部門, 准教授 (00283193)
• Co-Investigator(Kenkyū-buntansha): 稲谷 大 福井大学, 学術研究院医学系部門, 教授 (40335245) ; 沖 昌也 福井大学, 学術研究院工学系部門, 教授 (60420626)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: エピジェネティクス / 虚血 / サイトカイン / VEGF

Outline of Final Research Achievements

The central retinal thickness (CRT) before injection was subtracted from the CRT one month after injection to obtain the amount of edema improvement, and cases in which 80% or more of the CRT was reduced were considered good cases, while those in which only 20% or less was reduced were considered poor cases. Seven of the 12 cases were good and five were poor. Although cytokine levels decreased overall as the number of injections increased, certain cytokines were elevated in the failure cases, and epigenetic factors regulating their expression were identified. Residual areas showed lower microaneurysm (MA) density compared to resorptive areas; faricimab reduced the number of MAs as well as edema improvement and suppressed the development of new MAs. This was thought to be due to inhibition of both VEGF and Angiopoietin-2, which is associated with vascular stability.

Free Research Field

眼科　網膜

Academic Significance and Societal Importance of the Research Achievements

難治性の糖尿病黄斑浮腫の症例におけるサイトカインや遺伝子の発現パターンの特徴がわかり、さらに同じ抗VEGF薬であっても、製剤ごとに変動する遺伝子プロファイルが異なることが示された。エピジェネティックな制御を行うことで、これまで不可能とされた虚血領域の縮小の治療の可能性が示唆されるデータをえることが出来た。