Molecular mechanisms of inner retinal neurodegeneration and development of novel therapies

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22692
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Keio University
• Principal Investigator: Kunimi Hiromitsu 慶應義塾大学, 医学部(信濃町), 特任助教 (40877073)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: HIF-1α / BNIP3 / 眼虚血再灌流 / 網膜神経節細胞 / 緑内障

Outline of Final Research Achievements

The purpose of this study was to elucidate the molecular mechanisms of retinal nerve cell death in diseases that cause nerve cell damage in the inner retina, including glaucoma, the leading cause of blindness in Japan, and to develop new treatments for such diseases.
Using an animal model of neurodegeneration of the inner retina, we discovered hypoxia-inducible factor 1α (HIF-1α) and its downstream gene, BNIP3, among about 100 genes, as the causative genes for neuronal cell death in the inner retina. We also found that inhibition of this BNIP3 gene in the retina had a neuroprotective effect even when the same damage was inflicted on the retina.
These results suggest that BNIP3 inhibition may be useful in the novel treatment of glaucoma.

Free Research Field

網膜神経細胞

Academic Significance and Societal Importance of the Research Achievements

本研究の最終目的である緑内障に対する新規治療開発について、HIF-1α/BNIP3経路の阻害という新しい可能性を見出すことができた。本邦の失明原因第一位である緑内障治療は、現在のところ点眼、手術ともに眼圧下降という対症療法のみであり、根本的な新規治療開発が待たれる状況である。網膜神経節細胞という網膜内層にある細胞が細胞死を引き起こすことで緑内障が発症するが、その分子メカニズムを解明でき、かつ動物モデルでも証明できたことは今後ヒトでの治療法開発につながると考えられる。