Prevention research for diabetic retinopathy based on structure-activity relationship study of novel polymethoxyflavones

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860067
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Teikyo University
• Principal Investigator: MIYATA Yoshiki 帝京大学, 薬学部, 講師 (20433881)
• Co-Investigator(Renkei-kenkyūsha): OSHITARI Tetsuta 帝京大学, 薬学部, 教授 (00279043)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: フラボノイド / ミュラー細胞 / 糖尿病網膜症 / 小胞体ストレス / マトリックスメタロプロテアーゼ

Outline of Final Research Achievements

Muller cells are a crucial component of the retinal tissue performing a wide range of functions including maintaining retinal structure. In diabetic retinopathy, hyperglycemia induces the dysfunction of Muller cells. We examined the mechanism of diabetes-induced overexpression of matrix metalloproteinases (MMP) and cell death in Muller cells. In addition, we examined the effect of nobiletin and the derivatives. Nobiletin could suppress proMMP-9 production and augment the production of TIMPs which are MMP endogenous inhibitors. Furthermore, we found that ER stress was one of key inducers involved in apoptotic cell death of Muller cells. Nobiletin was found to show anti-apoptotic action on the ER stress-induced Muller cell death. Through structure-activity relationship study, we clarified the structural feature related to the anti-MMP or apoptotic action by nobiletin. In addition, we found novel flavones with stronger inhibitory action on MMP production compared with nobiletin.

Free Research Field

薬物治療学