Regulation of experimental autoimmune uveoretinitis through Nrf2 signaling

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyorin University
• Principal Investigator: Keino Hiroshi 杏林大学, 医学部, 准教授 (90328211)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ぶどう膜炎

Outline of Final Research Achievements

Oxidative stress is a major factor in the development of various ocular diseases. Nuclear factor erythroid 2 related factor 2 (Nrf2) is known to be a key transcription factor in the regulation of multiple anti-oxidants including hemeoxygenase-1 (HO-1) and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) quinine oxidoreductase 1 (NQO1). In the current study, we investigated the effect of Nrf2 on the development of EAU using Nrf2 knock out (KO) mouse. Pathological analysis of ocular lesion from Nrf2 KO mice with EAU revealed more severe infiltration of inflammatory cells into vitreous/retina and retinal tissue damages compared to that from wild type mice. Pathological score of EAU was higher in Nrf2 KO mice than wild type mice, although there was no significant difference between Nrf2 KO mice and wild type mice. Further study is required to determine the association between oxidative stress and the pathogenesis of autoimmune uveoretinitis.

Free Research Field

ぶどう膜炎

Academic Significance and Societal Importance of the Research Achievements

本研究課題ではぶどう膜炎における酸化ストレスとの関連に注目し、抗酸化ストレス分子誘導因子として知られるNrf2の関与について明らかにするためNrf2欠損(KO)マウスにEAUを誘導し、酸化ストレスとぶどう膜炎との関連について検討を行った。その結果、野生型マウスと比較して、Nrf2KOマウスにおいて病理組織像の重症化が観察された。Nrf2を介した抗酸化ストレス機構の破綻が眼内の炎症病態に関与している可能性、さらに酸化ストレス機構がぶどう膜炎の新たな治療標的となる可能性が示唆された。