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大鼠光诱导视网膜损伤相关的簇集素表达变化

Changes in clusterin expression associated with light-induced retinal damage in rats.

作者信息

Wong P, Kutty R K, Darrow R M, Shivaram S, Kutty G, Fletcher R T, Wiggert B, Chader G, Organisciak D T

机构信息

National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Biochem Cell Biol. 1994 Nov-Dec;72(11-12):499-503. doi: 10.1139/o94-067.

Abstract

Prolonged periods of high-intensity visible light exposure lead to photoreceptor cell degeneration, but the mechanism of damage is not understood. Increased clusterin mRNA levels have been found in several models of apoptosis, as well as in neurodegeneration. We report here that changes in clusterin mRNA levels are also associated with light-induced retinal damage in adult male albino rats. Animals previously maintained in darkness or a weak cyclic light environment were exposed to intense visible green light for up to 24 h. Some rats were pretreated with a synthetic antioxidant, dimethylthiourea (DMTU), which reduces photoreceptor cell degeneration. Clusterin mRNA steady-state levels increased with the duration of light exposure in both cyclic light and dark reared animals, suggesting that an apoptotic mechanism may be involved. Animals pretreated with DMTU showed a delay in the initial increase in clusterin mRNA levels, suggesting that oxidative damage is involved in the damage mechanism. However, the incomplete suppression of increasing steady-state clusterin mRNA levels by DMTU suggests that either oxidative damage triggers a second pathway or multiple damage mechanisms are induced in the retina by light exposure.

摘要

长时间高强度可见光照射会导致光感受器细胞退化,但其损伤机制尚不清楚。在几种细胞凋亡模型以及神经退行性变中均发现簇集素(clusterin)mRNA水平升高。我们在此报告,簇集素mRNA水平的变化也与成年雄性白化大鼠的光诱导视网膜损伤有关。先前饲养在黑暗或弱循环光照环境中的动物,暴露于强烈的可见绿光下长达24小时。一些大鼠用合成抗氧化剂二甲基硫脲(DMTU)进行预处理,DMTU可减少光感受器细胞退化。在循环光照和黑暗饲养的动物中,簇集素mRNA稳态水平均随光照时间的延长而增加,这表明可能涉及凋亡机制。用DMTU预处理的动物,簇集素mRNA水平的初始升高出现延迟,这表明氧化损伤参与了损伤机制。然而,DMTU对簇集素mRNA稳态水平升高的不完全抑制表明,要么氧化损伤触发了第二条途径,要么光照在视网膜中诱导了多种损伤机制。

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