Adrenal and Glucocorticoid Effects on the Circadian Rhythm of Murine Intraocular Pressure.
Adrenal and Glucocorticoid Effects on the Circadian Rhythm of Murine Intraocular Pressure.
复制标题
肾上腺和糖皮质激素对小鼠眼压昼夜节律的影响。
DOI：
10.1167/iovs.18-24785
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发表时间：
2018
影响因子：
4.4
通讯作者：
VanGelder,RussellN
中科院分区：
文献类型：
--
作者：
Tsuchiya,Shunsuke;Sugiyama,Kazuhisa;VanGelder,RussellN
目的：眼压(IOP)随强烈的昼夜节律波动，这种昼夜节律通过位于视交叉上核团的主昼夜节律与机体节律同步。目前尚不清楚视交叉上核团与眼压节律之间维持昼夜节律同步的机制。本研究的目的是评价肾上腺和糖皮质激素功能对虹膜睫状体夹带和眼压昼夜节律的必要性和充分性。方法：取C57BL/6J小鼠，每隔3小时置于12小时的光/暗周期中，解剖虹膜-CB复合体，并对其核心时钟基因(PER1、PER2和BMal1)和糖皮质激素受体mRNA的表达进行定量。解剖和培养Perio2：：荧光素酶小鼠的Iris-CB复合体，以测定体外节律性。为了确定糖皮质激素对虹膜-CB的相移效应，在特定的昼夜节律时向培养组织中加入地塞米松或赋形剂。结果：在虹膜-CB复合体中，糖皮质激素受体mRNA的表达全天保持稳定，而核心时钟基因的mRNA表达具有较强的昼夜节律性。当地塞米松在昼夜时间8(CT8)到CT12之间给药时，显著地引起相延迟，而当在CT16到CT20之间给药时，则显著地引起相提前。肾上腺切除消除了眼压昼夜节律性，尤其是降低了夜间眼压升高。结论：糖皮质激素足以使虹膜-CB的昼夜节律发生相移。小鼠眼压的昼夜节律需要完整的肾上腺功能。综上所述，这些数据与糖皮质激素调节眼压到昼夜节律振荡器的假设是一致的。
Purpose: Intraocular pressure (IOP) fluctuates with a robust circadian rhythm, which is synchronized to organismal rhythmicity through the master circadian clock located in the suprachiasmatic nuclei. The mechanisms maintaining circadian synchrony between the suprachiasmatic nuclei and IOP rhythms are presently unknown. The purpose of this study was to evaluate the necessity and sufficiency of adrenal and glucocorticoid function for the entrainment of iris-ciliary body (iris-CB) and IOP circadian rhythms in mice.Methods: Iris-CB complexes were dissected from C57Bl/6J mice that were kept in 12-hour light/dark cycles at 3-hour intervals, and their core clock gene (Per1, Per2, and Bmal1) and glucocorticoid receptor mRNA expression were quantified. Iris-CB complexes from period2:: luciferase mice were dissected and cultured to measure in vitro rhythmicity. To determine the phase-shifting effect of glucocorticoids on the iris-CB, dexamethasone or vehicle was added to the cultured tissues at defined circadian phases. The diurnal IOP rhythms of adrenalectomized or sham-operated mice under the 12-hour light/dark cycles were also measured.Results: In iris-CB complexes, glucocorticoid receptor mRNA expression remained stable throughout the day, whereas the mRNA of core clock genes showed a robust circadian rhythmicity. Dexamethasone significantly induced phase-delays when administered between circadian time 8 (CT8) to CT12 and phase-advance when given between CT16 to CT20. Adrenalectomy abolished circadian IOP rhythmicity, particularly diminishing nocturnal IOP elevation compared with sham-operated mice.Conclusions: Glucocorticoids are sufficient for phase shifting the circadian clock in iris-CB. Intact adrenal function is required for manifest circadian rhythms of IOP in mice. Taken together, these data are consistent with the hypothesis that glucocorticoids mediate circadian entrainment of IOP to the master circadian oscillator.