Circadian intraocular pressure rhythm is generated by clock genes

Circadian intraocular pressure rhythm is generated by clock genes
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DOI:
10.1167/iovs.06-0183
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发表时间:
2006-09-01
影响因子:
4.4
通讯作者:
Sugiyama, Kazuhisa
Sugiyama, Kazuhisa
中科院分区:
医学2区
文献类型:
--
作者:
Maeda, Ari;Tsujiya, Sosuke;Sugiyama, Kazuhisa

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目的.本研究通过小鼠模型揭示了生物钟基因Cry 1和Cry 2在24小时眼内压(IOP)节律产生中的作用。每天在8个时间点(昼夜节律时间[CT] 0、3、6、9、12、15、18和21小时)使用显微针法在4组C57 BL/6 J小鼠(第1组和第3组,野生型;第2组和第4组,Cry缺陷[Cry 1(-/-)Cry 2(-/-)])中测量IOP。在IOP测量期间,将第1组和第2组中的小鼠保持在12小时明-暗循环(LD)中,而将第3组和第4组中的小鼠保持在测量前24至48小时开始的恒定黑暗(DD)中。通过单因素方差分析(ANOVA)和Scheffe检验评估各组的昼夜IOP变化。在生活在LD条件下的野生型小鼠中,在光照阶段测量的压力显著低于黑暗阶段。在DD条件下维持这种每日节律,主观白天低压,主观夜晚高压。相反,Cry缺陷小鼠没有表现出显著的昼夜变化的眼内压,无论环境光条件。这些研究结果表明,时钟振荡机制需要核心时钟基因的活动是必不可少的产生昼夜节律的眼内压。
PURPOSE. The present study in a mouse model was undertaken to reveal the role of the circadian clock genes Cry1 and Cry2 in generation of 24-hour intraocular pressure (IOP) rhythm.METHODS. IOP was measured at eight time points daily (circadian time [CT] 0, 3, 6, 9, 12, 15, 18, and 21 hours), using a microneedle method in four groups of C57BL/6J mice (groups 1 and 3, wildtype; groups 2 and 4, Cry-deficient [Cry1(-/-) Cry2(-/-)]). During the IOP measurements, mice in groups 1 and 2 were maintained in a 12-hour light-dark cycle (LD), whereas mice in groups 3 and 4 were kept in a constant darkness ( DD) that started 24 to 48 hours before the measurements. Circadian IOP variations in each group were evaluated by one-way analysis of variance (ANOVA) and Scheffe tests.RESULTS. In wild-type mice living in LD conditions, pressures measured in the light phase were significantly lower than those in the dark phase. This daily rhythm was maintained under DD conditions with low pressure in the subjective day and high pressure in the subjective night. In contrast, Cry-deficient mice did not show significant circadian changes in IOP, regardless of environmental light conditions.CONCLUSIONS. These findings demonstrate that clock oscillatory mechanisms requiring the activity of core clock genes are essential for the generation of a circadian rhythm of intraocular pressure.