Entrainment of circadian rhythm to a photoperiod reversal shows retinal dystrophy in RPE65-/- mice

Entrainment of circadian rhythm to a photoperiod reversal shows retinal dystrophy in RPE65-/- mice
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DOI:
10.1016/s0031-9384(03)00202-6
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发表时间:
2003-09-01
影响因子:
2.9
通讯作者:
Rakoczy, PE
Rakoczy, PE
中科院分区:
医学3区
文献类型:
--
作者:
Daniels, DM;Stoddart, CW;Rakoczy, PE

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昼夜节律的光夹带是由经典的“视觉”光感受器(杆和锥)以及“非视觉”光感受元件(光检测细胞,不有助于经典的“视觉”)介导。本文旨在评估视杆细胞和视锥细胞受损的小鼠的运动昼夜节律的光诱导是否与正常对照不同,以及这种技术与现有技术一起是否可用于评估视觉功能。该研究主要关注视力正常的C57 BI/6 J小鼠和C57 B1/RPE 65敲除小鼠(RPE 65(-/-))的昼夜节律的诱导之间的差异,尽管C3 H/HeJ(rd/rd)小鼠被包括作为视网膜变性的预先存在的模型。在持续监测运动的定制笼子中评估了12小时光逆转前后运动活动的昼夜节律。当与RPE 65(-/-)和rd/rd小鼠相比时,对照显示出显著更高的介量和振幅。尽管失去了视杆细胞和视锥细胞,RPE 65(-/-)和rd/rd保持了24小时的昼夜节律,类似于对照组的光诱导,并能够昼夜节律再诱导到12小时的光逆转。重要的是,视网膜退化模型中昼夜节律时相的光再夹带发生的速率明显低于对照组。与rd/rd模型相比,RPE 65(-/-)模型证明了视网膜变性再夹带表型。这表明,这些视网膜退化的小鼠保留的能力,以检测光的昼夜节律夹带的目的。然而,随着视杆细胞和视锥细胞的丧失,昼夜节律的特定参数的改变可以提供视觉功能(视力)丧失的测量。(C)2003年爱思唯尔公司All rights reserved.
Light entrainment of circadian rhythms is mediated by classical "visual" photoreceptors (rods and cones) as well as "nonvisual" photoreceptive elements (light-detecting cells that do not contribute to classical "vision"). This paper aimed to assess whether light entrainment of locomotor circadian rhythms in mice with impaired rods and cones differs from normal controls and whether this technique, alongside existing techniques, could be used to assess visual function. The study was primarily interested in differences between the entrainment of circadian rhythms of normal-sighted C57BI/6J mouse and the C57B1/RPE65 knockout mouse (RPE65(-/-)), although C3H/HeJ (rd/rd) mice were included as a preexisting model of retinal degeneration. Circadian rhythms of motor activity before and after a 12-h light reversal were assessed in custom-built cages that continuously monitored movement. The controls showed a significantly higher mesor and amplitude when compared to the RPE65(-/-) and rd/rd mice. Despite the loss of rods and cones, the RPE65(-/-) and rd/rd maintained a 24-h circadian rhythm entrained to light similar to controls and were capable of circadian reentrainment to a 12-h light reversal. Importantly, this light reentrainment of the circadian phase occurred at a significantly slower rate in the retinal degenerate models than in the controls. The RPE65(-/-) model demonstrates a retinal degenerate reentrainment phenotype when compared to the rd/rd model. It is suggested that these retinal degenerate mice retain the ability to detect light for the purposes of circadian rhythm entrainment. However, alterations of specific parameters of the circadian rhythm with loss of rods and cones may provide measures of loss of visual function (sight). (C) 2003 Elsevier Inc. All rights reserved.