Metabolic Plasticity in Cell State Homeostasis and Differentiation of Cultured Human Corneal Endothelial Cells as A New Target for Drug Development

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670759
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: SOTOZONO CHIE 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30216585)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 角膜内皮細胞 / エネルギー代謝応答 / 解糖系 / ミトコンドリア / 代謝リモデリング / miRNA / 細胞相転移

Outline of Final Research Achievements

In this　study, we found the way, using the culture supernatants, to　discrimiーnate SPs in cHCECs in terms of their secretory metabolites, and found that the CST SPs exhibited the disposition to the anaerobic glycolysis instead of mitoc-hondria-dependent OXPHOS. The study on the secretory metabolites assigned the cHCEC SPs distinct in the expression levels of surface CD44 antigen. Transition from oxidative metabolism into glycolysis is a prerequisite for reprogramming to the pluripotent state. Conversely, redirection of pluripotency into defined lineages requires　mito- chondrial biogenesis and maturation of efficient oxidative energy generati- on.The reduction of glycolysis might be triggered by downregulation of the cMyc pathway.Our novel findings provide evidence of a possible link between metabo-lic regulation in the corneal endothelium and the development of more effective targeted therapies to treat patients with bullous keratopathy, including FECD.

Free Research Field

眼科学