Glial activation induced by unsaturated aldehyde acrolein in diabetic retinopathy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09393
• 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: Hokkaido University
• Principal Investigator: Noda Kousuke 北海道大学, 医学研究院, 准教授 (90296666)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 網膜グリア細胞 / 不飽和アルデヒド / 糖尿病網膜症

Outline of Final Research Achievements

Diabetic retinopathy (DR) is a retinal microvascular complication of diabetes and is still a leading cause of visual impairment in the developed countries.　Previous studies revealed that retinal glial cell migration is involved in the fibrovascular tissue formation, leading to the severe complications in patients with DR; however, the detailed mechanisms remains unclear.
Acrolein is a highly reactive unsaturated aldehyde that causes dysfunction of multiple proteins. In this study, we explored the regulatory mechanisms responsible for retinal glial cell migration induced by unsaturated aldehyde acrolein and found that i) acrolein exerted potent cellular toxicity at a high concentration; however, sublethal concentration of acrolein slightly induces viability and migratory property of retinal glial cells; and ii) inflammatory chemokine CXCL1 is a mediator of glial cell migration induced by acrolein.

Free Research Field

網膜硝子体疾患

Academic Significance and Societal Importance of the Research Achievements

近年、糖尿病網膜症の病態は少しずつ明らかとされ、同疾患に関する理解の蓄積、そしてその結果として糖尿病黄斑浮腫治療に臨床導入されたVEGF阻害剤の開発は糖尿病網膜症の治療体系を大きく変えた。しかしその一方で、糖尿病網膜症の病態、特に線維血管組織の形成メカニズムには不明な点が未だ多く存在する。本研究は、線維血管組織の形成に重要な役割を演じると考えられている網膜グリア細胞の遊走メカニズムについて検討を行い、その一部を明らかとした。