Development of retinal disease regulation from prevention to therapeutic technology targeting hypoxia responses

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09424
• 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: Keio University
• Principal Investigator: KURIHARA Toshihide 慶應義塾大学, 医学部(信濃町), 講師 (50365342)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 網膜 / 低酸素 / 血管新生 / 神経変性

Outline of Final Research Achievements

We aimed to establish anti-HIF therapies in order to prevent various ocular diseases and systemic malfunction. We have reported the therapeutic effect of a known HIF inhibitor topotecan in murine oxygen-induced retinopathy and ischemic reperfusion models. Furthermore, novel HIF inhibitors including halofuginone, hydroxycitric acid, lactoferrin, fish ingredients, vitamin B6, and fenofibrate have been screened. We have reported their therapeutic effects verified with various animal models. In addition, we have reported functions of a non-visual photoreceptor OPN5 in myopia progression inspired by the report of hypoxia response playing a role in myopia by another research group abroad.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

研究開始前までに得られた異常な低酸素応答による網膜での病態形成知見を基に、食物由来因子ライブラリを用いた新たなスクリーニングを実施し、新規HIF阻害物質の同定ならびに、その治療効果を様々な動物モデルで検証した。本研究で得られた候補物質はいずれも日常的に摂取可能な機能性食品やサプリメントとして活用できる可能性があり、加齢黄斑変性のみならず糖尿病網膜症などの他の血管新生網膜疾患の治療、個体そのものの機能低下に対して、安全に介入できる可能性を見出した。また近視進行抑制の機序に関しても本研究を基に明らかとし、今後多くの臨床的な応用が期待できる成果を得た。