Van Gelder Russell N, Sancar Aziz
Department of Ophthalmology and Visual Sciences, Washington University Medical School, CB# 8096, 660 S. Euclid Avenue, St Louis, MO 63110, USA.
Novartis Found Symp. 2003;253:31-42; discussion 42-55, 102-9, 281-4.
Nearly all circadian clocks have free-running periods that differ significantly from 24 hours. To maintain synchrony with the 24 h day, the mammalian circadian clock is reset by light. Unlike other animals, mammalian circadian entrainment occurs exclusively via the eyes and optic nerves. Remarkably, the classical photoreceptors--the rods and cones--are not necessary for photic entrainment. Instead, a subset of inner retinal ganglion cells are directly photoresponsive and transmit photic information specifically to brain centres involved in irradiance detection, including the master circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus. The photopigment(s) responsible for inner retinal phototransduction are unknown. Several lines of evidence constrain candidate photopigments. First, near-total vitamin A depletion does not diminish retinohypothalamic signalling. Second, loss of cryptochrome function in retinal-degenerate mice substantially decreases photic signalling to the suprachiasmatic nucleus, and markedly decreases pupillary light responses. Third, vitamin A depletion of cryptochrome mutant mice leads to loss of photic signalling to the suprachiasmatic nucleus. These findings suggest a model where either classical photopigments or inner retinal photopigments are sufficient for non-visual irradiance detection.
几乎所有的生物钟都有与24小时显著不同的自由运转周期。为了与24小时的一天保持同步，哺乳动物的生物钟会被光重置。与其他动物不同，哺乳动物的昼夜节律调节完全通过眼睛和视神经进行。值得注意的是，经典的光感受器——视杆细胞和视锥细胞——对于光调节并非必需。相反，一部分视网膜内神经节细胞直接对光有反应，并将光信息特异性地传递到参与辐照度检测的脑中枢，包括下丘脑视交叉上核中的主生物钟起搏器。负责视网膜内光转导的光色素尚不清楚。几条证据限制了候选光色素。首先，几乎完全耗尽维生素A并不会减少视网膜下丘脑信号传导。其次，视网膜退化小鼠中隐花色素功能的丧失会大幅降低向视交叉上核的光信号传导，并显著降低瞳孔对光反应。第三，隐花色素突变小鼠的维生素A耗尽会导致向视交叉上核的光信号传导丧失。这些发现提示了一个模型，即经典光色素或视网膜内光色素对于非视觉辐照度检测都是足够的。
