2001 Fiscal Year Final Research Report Summary
RESEACH FOR THE PATHOGENESIS OF DIABETIC RETINOPATHY
| Project/Area Number |
12671106
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Nagoya University |
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Principal Investigator |
HAMADA Yoji University Hospital, Nagoya University, Research Associate, 医学部・附属病院, 助手 (20293706)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Eitaro University Hospital, Nagoya University, Research Associate, 医学部・附属病院, 助手 (50335030)
NAKAMURA Jiro Graduate School of Medicine, Nagoya University, Associate Professor, 大学院・医学研究科, 助教授 (40283444)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Diabetic Complications / Retinal MicrovascuLar Pericytes / Apoptosis / Poiyol Pahtway / Protein Kinase C / Oxidentive Stress / Aldose Reductase Inhibitior |
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| Research Abstract |
The mechanisms of the glucose-induced apoptosis in retinal pericytes were investigated to evaluate the pathogenesis of diabetic retinopathy. Under the 20 mM glucose condition, intracellular calcium concentrations and caspase-3 activities were significantly increased, and reduced glutathione contents and PKC activities were significantly decreased, compared with those under the 5. 5 mM glucose condition. These abnormalities were all significantly prevented by an aldose reductase inhibitor, SNK-860. Glucose-induced apoptosis was partially but significantly prevented by SNK-860, a calpain inhibitor, or reduced glutathione supplementation, and completely normalized by a caspase-3 inhibitor. These observations suggest that glucose-induced apoptosis in retinal pericytes would be mediated through an aldose reductase sensitive pathway including caicium-calpain cascade, increased oxidative stress and decreased PKC activities, and that caspase-3 would be located furthest down stream of these apoptotic signals.
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