| Project/Area Number |
13671857
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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 |
Ophthalmology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
SENZAKI Hideto Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10206659)
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| Co-Investigator(Kenkyū-buntansha) |
YUGE Kenshi Kansai Medical University, Faculty of Medicine, Instructor, 医学部, 助手 (10247942)
SHIKATA Nobuaki Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00121939)
TSUBURA Airo Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (90098137)
HAGA Satomi Nara Medical University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20192263)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Retinitis pigmentosa / N-methyl-N-nitrosourea / Apoptosis / Hyperoxia / Photoreceptor cell / Nicoinamide / Mouse / Rat |
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| Research Abstract |
A single systemic administration of N-methyl-N-nitrosourea {MNU) to rats and mice resulted in retinal degeneration (RD) due to photoreceptor cell apoptosis in all treated animals over a 7-day period. Caspase-3 inhibitor partially suppressed MNU-induced RD in rats. We next tested the effect of hyperoxia, 95% O_2 with vasodilator nicotinamide (NAM), which NAM alone suppressed photoreceptor cell loss in a dose-dependent manner when administered immediately after MNU treatment. In rats, a dose of NAM【greater than or equal】25 mg/kg completely suppressed photoreceptor cell loss, and 10 mg/kg partially suppressed photoreceptor cell loss. In mice, doses of 1000 mg/kg and 【greater than or equal】100 mg/kg were needed for complete and partial suppression, respectively. The retinoprotective effect of 1000 mg/kg NAM lasted throughout the long-term (35 days) observation period, with no apparent toxicity. Also, in rats, 1000 mg/kg NAM completely suppressed photoreceptor cell loss when administered up to 4 hrs after MNU treatment, and partially suppressed photoreceptor cell loss when administered 6 hrs after MNU treatment In mice, administration of NAM 2 to 6 hrs after MNU resulted in partial suppression. NAM did not reduce levels of 7-methyldeoxyguanosine DNA adduct, but did reduce photoreceptor cell apoptosis. Although the mechanism of action underlying this retinoprotection remains to be clarified, NAM may be a potential therapeutic agent for the treatment of retinal degeneration.
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