Inhibition of angiogenesis and scarring at AMD pathology by epigenetic regulation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09831
• 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: Kyoto Prefectural University of Medicine
• Principal Investigator: Hiramoto Nao 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (10609093)
• Co-Investigator(Kenkyū-buntansha): 向 敦史 京都府立医科大学, 医学(系)研究科(研究院), 研究員 (00419152)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 加齢性黄斑変性症 / 網膜色素上皮細胞 / エピジェネティック制御 / 脈絡膜新生血管

Outline of Final Research Achievements

Co-culture of retinal pigment epithelial cells (RPE) and macrophages (Mps), a pathological model of age-related macular degeneration (AMD), and induction of fibrosis in RPE have been shown to enhance the production of many pro-angiogenic factors. Production of many of these factors was suppressed by OBP801 (OBP). This suggests the possibility that OBP suppresses degeneration of RPE and indirectly suppresses angiogenesis in AMD. On the other hand, experiments using a vascular endothelial cell culture system revealed that OBP acts directly on vascular endothelial cells and inhibits cell proliferation, migration, and tube formation. Furthermore, OBP exhibited a stronger inhibitory effect than existing anti-VEGF agents on tube formation induced by some pro-angiogenic factors. Based on these results, we believe that OBP can become a new treatment for AMD that surpasses existing drugs.

Free Research Field

応用細胞分子生物学

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性(AMD)は近年著しく増加中の重篤な視力障碍を引き起こす疾患である。現在主流の治療法である抗VEGF治療はCNV抑制にはある程度効果を示すが、抵抗性患者の存在や視力予後因子である網膜組織の線維化には効果がない等、いくつかの問題点がある。本課題ではOBPが直接および間接的に血管形成を阻害することを明らかにした。一方、我々の以前の研究では、OBPがRPEの線維性変化に対し抑制効果を持つことが確認されている。これらのOBPの作用効果の検証結果を以って、線維性組織形成阻害効果およびCNV抑制効果を併せ持つ、今までにない強力かつ斬新なAMD治療薬の開発が大きく前進すると言える。