| Project/Area Number |
08672036
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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 | Tokyo Women's Medical College |
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Principal Investigator |
KITANO Shigehiko Tokyo Women's Medical College・Medical School・Associate Professor, 医学部, 助教授 (30161483)
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| Co-Investigator(Kenkyū-buntansha) |
MOTEGI Yutaka Tokyo Women's Medical College・Medical School・Associate, 医学部, 助手 (80266717)
HORI Sadao Tokyo Women's Medical College・Medical School・Professor, 医学部, 教授 (20143498)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Retinal ganglion cell / Excitatory amino acid / Ischemia / Heat shock protein / Muller cell |
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| Research Abstract |
Knowledge of the mechanisms by which retinal ganglion cells are damaged may provide information required to develop novel treatments for diseases that cause retinal ganglion cell death. The authors investigated whether the expression of the 72-kDa heat shock protein in cultured rat retinal ganglion cells increases tolerance to hypoxic and excitotoxic injury.
Hyperthermia (42* far 1 hour) and sublethal hypoxia (10% 02 for 6 hours) were used to induce synthesis of the 72-kDa heat shock protein in cultured rat retinal ganglion cells and cultured retinal Muller cells. Induction of the 72.kDa heat shock protein was detected with immunocytochemical and immunoblot techniques. Survival of cultured retinal ganglion cells after exposure to anoxia (0% 02 for 6 hours) and glutamate (200 mum 6or 6 hours) was measured and compared to control cultures stressed previously by hyperthermia or sublethal hypoxia. The effect of quercetin, a blocker of heat shock protein synthesis, was evaluated in parallel
… More
experiments.
Heat shock protein immunoreactivity was expressed in cultured retinal ganglion cells and Muller cell after hyperthermia and sublethal hypoxia. The mean (* standard deviation) retinal ganglion cell survival rates after exposure to anoxia (expressed as a percentage of untreated control cultures) in cells pretreated with sublethal hypoxia (83% * 17%) and hyperthermia (82% * 19%) were significantly greater than for cells that had no pretreatment (50% * 18%, P <0.001). The mean (* standard deviation) retinal ganglion cell survival rate after exposure to glutamate in cells pretreated with sublethal hypoxia (82% * 19%) and hypcrthermia (86% * 17%) were significantly greater than for ceus that had no pretreatment (56% * 17%, P <0.001). Inhibition of heat shock protein synthesis with quercetin abolished the protective effects of sublethal hypoxia and hyperthermia on cell survival after anoxia and glutamate exposure.
The neuroprotective effect of hyperthermia and sublethal hypoxia suggests that heat shock proteins confer protection against ischemic and excitotoxic retinal ganglion cell death. Less
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