Role of complement factor MASP-1/3 in age-related macular degeneration and therapeutic effect of novel complement inhibitors

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16975
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Fukushima Medical University
• Principal Investigator: Omori Tomoko 福島県立医科大学, 医学部, 助教 (50754222)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 加齢黄斑変性 / 補体

Outline of Final Research Achievements

We aimed to clarify the role of complement factor MASP-1/3 of the lectin and alternative pathways in the development of neovascular age-related macular degeneration (nAMD). In patients with nAMD, the ratios of aqueous humor levels of C4a/C4 and C3a/C3 were significantly higher than in cataract patients, providing conclusive evidence for intraocular activation of the lectin and/or classical pathway in nAMD eyes. Furthermore, using mouse model of laser-induced choroidal neovascularization, which has been used extensively studies of nAMD, we found that the nAMD-like lesion was alleviated in mice deficient for MASP-1/3 compared to wild-type mice, although there was no significant difference between them. Our results strongly suggest the contribution of MASP-1/3 in the development of nAMD.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、第二経路に加え、眼内におけるレクチン経路と古典経路の一方または両方の活性化が滲出型加齢黄斑変性の病態に関与することが明らかとなった。よって、MASP-1/3を標的とする治療法が有効である可能性が強く示唆された。これらの成果は、滲出型加齢黄斑変性の病態における補体の関与への理解を深め、滲出型加齢黄斑変性の新規治療法や新規診断法の開発に繋がると期待される。