| Project/Area Number |
07557109
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Ophthalmology
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| Research Institution | Tohoku University |
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Principal Investigator |
TAMAI Makoto School of Medicine, Ophthalmology, Professor, 医学部, 教授 (90004720)
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| Co-Investigator(Kenkyū-buntansha) |
OHKI Kazuo Faculty of Science, Biophysics, Professor, 理学部, 教授 (80115394)
TAKEDA Atushi School of Medicine, Neurology, Assistant Pro f., 医学部, 助手 (70261534)
ISHIGURO Sei-ichi School of Medicine, Ophthalmology, Assistant Prof, 医学部, 講師 (20111271)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 1996: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1995: ¥12,700,000 (Direct Cost: ¥12,700,000)
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| Keywords | ischemia / retinal damage / cytokines / neurotrophic factors / growth factors / glutamate / excitotoxicity / liposomes |
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| Research Abstract |
Purpose :
Phosphate-activated glutaminase (PAG) activity decreases markedly in the early period of ischemia. The decrease of the enzyme activity is reversible if the ischemic period is relatively short, but it ibecomes irreversible after 90 minutes of ischemia. The deterioration is a functional damage of the retinas caused by ischemia. We studied effects of growth factors and neurotrophic factors on protection of PAG in the ischemic and reperfused rat retinas.
Methods :
Before ischemia, 1mul of growth factors or neurotrofic factors (0.1 mug/mul for insulin-like growth factor-l (IGF-I) , insulin-like growth factor-II (IGF-II) , brain-derived neurotrophic factor (BDNF) , nerve growth factor (NGF) ; 1 mug/mul for basic fibroblast growth factor (bFGF)) were injected into the vitreous cavity of the left eyes of anesthetized Sprague Dawley rats. As a control, phosphate buffered saline was injected to the right eyes. To induce ischemia, we clamped left eyes for 90 minutes after bulbar conjunctival incision all around limbus. The rat retinas were homogenized with distillled water 1 day after reperfusion and used for PAG assay. Retinal ammonia concentration was also determined as a ischemic marker.
Results :
About 80% decrease of retinal PAG activity and 50% increase of retinal ammonia concentration were observed after 90 minutes of ischemia and 1 day of reperfusion as compared with unoperated normal eyes. IGF-II,BDNF and NGF had protective effects on the retinal PAG activity, whereas IGF-I,bFGF,stable bFGF were less effective. In addition, IGF-II and BDNF suppressed elevation of retinal ammonia concentration.
Conclusions :
BDNF,NGF and IGF-II have marked effect on the protection of PAG activity in the ischemic and reperfused rat retinas, whereas bFGF,which is very effective for the protection of ischemic cell death, shows moderate effect.
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