Mechanism of soluble VAP-1/ SSAO production in diabetic retinopathy
Project/Area Number |
17K11444
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Ophthalmology
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Research Institution | Hokkaido University |
Principal Investigator |
|
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
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 糖尿病網膜症 / 血管内皮増殖因子 / マトリックスメタロプロテアーゼ / VAP-1/ SSAO / 眼細胞生物学 |
Outline of Final Research Achievements |
Diabetic retinopathy (DR) is a leading cause of severe vision impairment; therefore, the elucidation of pathological mechanisms of DR is an important task in the field of ophthalmology. VAP-1/ SSAO is an enzyme that generates aldehydes and hydrogen peroxide through oxidation of primary monoamines. In the previous studies, we found that levels of VAP-1/ SSAO are elevated in the vitreous fluid of patients with DR. In the current study, we showed that vascular endothelial growth factor (VEGF) increases VAP-1/SSAO secretion from retinal capillary endothelial cells via induction of MMP-2 and MMP-9 enzymatic activity, and thereby accelerates oxidative stress in the cells.
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Academic Significance and Societal Importance of the Research Achievements |
糖尿病網膜症は糖尿病罹病期間にともなってその発症率が急増する細小血管障害であり、世界的な高齢化にともなって糖尿病網膜症患者数も今後増加すると推測されている。我々は、これまで糖尿病網膜症の病態メカニズムにおける炎症と酸化ストレスの関与に着目して検討を進め、この両者に関連する分子VAP-1/SSAOを主な研究対象としてきた。本研究により、VEGFによる網膜血管内皮細胞からのVAP-1/SSAO分泌亢進の機序が明らかとなり、糖尿病網膜症の病態形成に関わる重要な知見を得ることができた。
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Report
(4 results)
Research Products
(19 results)