Mechanism of acrolein generation in diabetic retinopathy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Hokkaido University
• Principal Investigator: Murata Miyuki 北海道大学, 医学研究院, 特任助教 (50423752)
• Co-Investigator(Kenkyū-buntansha): 野田 航介 北海道大学, 医学研究院, 准教授 (90296666)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 眼細胞生物学 / 糖尿病網膜症 / アクロレイン / 酸化ストレス / VAP-1

Outline of Final Research Achievements

Vascular adhesion protein-1 (VAP-1) expresses in vascular endothelial cells and involved in inflammation as a leukocyte adhesion molecule. In addition to its role as an adhesion molecule, VAP-1 also has enzymatic activity as an amine oxidase. Acrolein is a highly reactive unsaturated aldehyde and is included in cigarettes and so on as an exogenous pollutant. Recently it has been shown that acrolein is also produced endogenously as a consequence of polyamine oxidation. We found that the levels of the acrolein-conjugated protein are elevated in the vitreous fluid of patients with diabetic retinopathy (DR). VAP-1 protein levels are also elevated in the vitreous fluid of DR patients and correlated with acrolein-conjugated protein levels. In this study, we showed that VAP-1 generates acrolein by oxidizing the spermine, a kind of polyamine.

Free Research Field

眼細胞生物学

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜症の病態形成には、炎症と酸化ストレスの亢進が重要な役割を果たす。本研究では、白血球接着分子として炎症を促進する分子であるVAP-1が、糖尿病網膜症患者の硝子体中で増加するスペルミンを基質として不飽和アルデヒドであるアクロレインを生成し、酸化ストレスの亢進にも関与することを明らかにした。本研究により糖尿病網膜症の病態形成の新たなメカニズムが明らかになり、新規治療法の開発につながる重要な知見を得ることができた。