Controlling hypoxia-induced cell death for the treatment of retinal Degeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18393
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Keio University
• Principal Investigator: Miwa Yukihiro 慶應義塾大学, 医学部(信濃町), 特任助教 (30870430)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 低酸素誘導因子 / Hypoxia-inducible Factor / HIF / 網膜変性 / 網膜病的血管新生 / HIF-1α / 低酸素応答 / 網膜

Outline of Final Research Achievements

Our research focused on investigating the efficacy of novel treatment approaches for refractory retinal diseases. Specifically, we explored the involvement of hypoxia-inducible factor (HIF) in the pathogenesis of various mouse models of retinal degeneration. Through our investigations, we discovered that targeting HIF could yield therapeutic benefits in these disease models. Additionally, we shed light on the potential molecular mechanism involving the HIF-1α/BNIP3 axis. Furthermore, our study involved a screening of a natural product library to identify potential HIF inhibitors. Remarkably, we found that various food-derived extracts exhibited significant HIF inhibitory activity. We subsequently evaluated the effects of several novel HIF inhibitors obtained from this screening process in mouse models of refractory retinal diseases. Encouragingly, our findings demonstrated the inhibitory effects of these compounds on retinal neurodegeneration and pathological angiogenesis.

Free Research Field

網膜変性

Academic Significance and Societal Importance of the Research Achievements

網膜色素変性や萎縮型加齢黄斑変性などの網膜変性疾患は、網膜視細胞死を特徴とする難治性網膜疾患である。現在までに、確立された治療法や予防法は存在せず、我が国における中途失明原因の20%超を占める。その社会的コストは20兆円とされており、早急な治療法の確立が求められている。
本研究で得られた新規HIF阻害剤は、その多くが食品物に由来することからその安全性が担保されている。また、日常の食事に取り入れることが可能であると考えられることから、本研究で得られた新規HIF阻害剤は、より初期の網膜変性疾患に対し、より長期に渡って介入できる可能性を有している。