Pathomechanisms of mouse models of optic neuropathy by integrated omics analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09964
• 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: Tohoku University
• Principal Investigator: Sato Kota 東北大学, 医学系研究科, 助教 (50732327)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 緑内障 / オミックス

Outline of Final Research Achievements

In this study, we performed a comprehensive analysis of metabolites and mRNAs in vivo and an integrated omics analysis to comprehensively interpret. The results were used to predict the dynamics of abnormal retinal ganglion cell metabolism in optic neuropathy, which has been reported to be associated with retinal ganglion cell death in animal models of glaucoma. We aimed to investigate the reduced activity of Nrf2, which was reported to involve retinal ganglion cell death. RNA-seq results showed no reduction in Nrf2 expression or downstream Nqo1 expression. On the other hand, decreased glucose and decreased expression of a group of genes related to the glycolytic system occurred, suggesting decreased energy production due to attenuation of the glycolytic system in retinal ganglion cells during optic nerve crush.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

緑内障の根本的な発症原因は高眼圧であり、眼圧下降治療以外に有効な治療がない。一方で、眼圧下降治療が有効ではない患者も少なからず存在することから、眼圧下降治療に対して抵抗性を示す患者群の病態解明は特に重要な課題である。本研究では、眼圧非依存的な網膜神経節細胞死に解糖系の代謝異常が関与することを示唆する重要な知見であり、新たな治療法開発への応用が期待される。