Unmet Needs in the Beyond VEGF Era: Macrophage Educational Therapy for Retinal Fibrosis and Ischemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11456
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: Nakao Shintaro 九州大学, 医学研究院, 講師 (50583027)
• Co-Investigator(Kenkyū-buntansha): 園田 康平 九州大学, 医学研究院, 教授 (10294943) ; 吉田 茂生 久留米大学, 医学部, 教授 (50363370)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 糖尿病網膜症 / 加齢黄斑変性 / マクロファージ

Outline of Final Research Achievements

In a retinal ischemia mouse model, we observed infiltration of M1and M2 macrophages and increased expression of M1and M2 marker at mRNA level. We also observed that M1 macrophages were significantly present in the ischemic area. Gadolinium chloride, which mainly deletes M1 macrophages, was found to improve ischemia, suggesting that M1 macrophages could be a therapeutic target for retinal ischemia.
Fate mapping analysis in a subretinal fibrosis mouse model revealed that myofibroblast, which is a major component of fibrosis, is derived from RPE. The process involves epithelial-mesenchymal transition via ROCK suggesting that ROCK is a candidate drug for molecular target of subretinal fibrosis.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜症や加齢黄斑変性などの網膜疾患は近年抗VEGF療法の汎用により失明を免れる症例も増えてきた。しかし、抗VEGF療法においても治癒しない網膜虚血、網膜下線維化は現在のUnmet needsと言える。本研究はこれらの細胞レベルでのメカニズムを一部明らかにした。また今後の治療開発への一助となると考える。