Chong N W, Cassone V M, Bernard M, Klein D C, Iuvone P M
National Institutes of Health Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, 49/5A38, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Brain Res Mol Brain Res. 1998 Oct 30;61(1-2):243-50. doi: 10.1016/s0169-328x(98)00219-8.
Many aspects of retinal physiology are controlled by a circadian clock located within the eye. This clock controls the rhythmic synthesis of melatonin, which results in elevated levels during the night and low levels during the day. The rate-limiting enzyme in melatonin biosynthesis in retina appears to be tryptophan hydroxylase (TPH)[G.M. Cahill and J.C. Besharse, Circadian regulation of melatonin in the retina of Xenopus laevis: Limitation by serotonin availability, J. Neurochem. 54 (1990) 716-719]. In this report, we found that TPH mRNA is strongly expressed in the photoreceptor layer and the vitread portion of the inner nuclear layer; the message is also expressed, but to a lesser extent, in the ganglion cell layer. The abundance of retinal TPH mRNA exhibits a circadian rhythm which persists in constant light or constant darkness. The phase of the rhythm can be reversed by reversing the light:dark cycle. In parallel experiments we found a similar pattern of expression in the chicken pineal gland. However, whereas a pulse of light at midnight suppressed retinal TPH mRNA by 25%, it did not alter pineal TPH mRNA, suggesting that there are tissue-specific differences in photic regulation of TPH mRNA. In retinas treated with kainic acid to destroy serotonin-containing amacrine and bipolar cells, a high amplitude rhythm of TPH mRNA was observed indicating that melatonin-synthesizing photoreceptors are the primary source of the rhythmic message. These observations provide the first evidence that chick retinal TPH mRNA is under control of a circadian clock.
视网膜生理学的许多方面受位于眼内的昼夜节律时钟控制。该时钟控制褪黑素的节律性合成，导致夜间水平升高而白天水平降低。视网膜中褪黑素生物合成的限速酶似乎是色氨酸羟化酶（TPH）[G.M. 卡希尔和J.C. 贝沙尔塞，非洲爪蟾视网膜中褪黑素的昼夜节律调节：受血清素可用性的限制，《神经化学杂志》54（1990）716 - 719]。在本报告中，我们发现TPH mRNA在光感受器层和内核层的玻璃体侧部分强烈表达；该信息在神经节细胞层也有表达，但程度较轻。视网膜TPH mRNA的丰度呈现昼夜节律，在持续光照或持续黑暗中持续存在。通过颠倒明暗周期可使节律的相位反转。在平行实验中，我们在鸡松果体中发现了类似的表达模式。然而，午夜的一个光脉冲使视网膜TPH mRNA降低了25%，但并未改变松果体TPH mRNA，这表明在TPH mRNA的光调节方面存在组织特异性差异。在用 kainic 酸处理以破坏含血清素的无长突细胞和双极细胞的视网膜中，观察到TPH mRNA的高振幅节律，表明合成褪黑素的光感受器是节律性信息的主要来源。这些观察结果提供了首个证据，证明鸡视网膜TPH mRNA受昼夜节律时钟的控制。
