The mechanism of inhibitional effect to subretinal fibrosis by nuclear receptor system

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462663
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Yamaguchi University
• Principal Investigator: KIMURA Kazuhiro 山口大学, 医学(系)研究科(研究院), 教授 (60335255)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: retina / fibrosis / nuclear receptor / transcription factor / RPE cell

Outline of Final Research Achievements

In this study, the purpose is that formation and contraction of the subretinal fibrosis will be clarified focused on role of nuclear receptors in retinal pigment epithelial cells and we will develop novel therapeutic drugs based on transcriptional regulation through nuclear receptors.
We have screened ligands of nuclear receptors thorough three-dimensional culture system using retinal pigment epithelial cells. As a result, we identified steroid hormones containing glucocorticoid and a female hormone. These compounds were found to inhibit gel contraction. They also suppressed the expression of alpha SMA as a marker in EMT and the expression and activation of MMPs contributed to the remodeling of extracellular matrix. Their action was partially dependent on the signaling pathway of MAPKs or NF-κB. Furthermore, ATRA, vitamin A derivative, showed the same effect as steroids. Currently, we have been studying which receptors are specific for the action of vitamin A.

Free Research Field

眼科学