Photic and circadian regulation of retinal melatonin.

描述(申请人提供)：在哺乳动物的视网膜中存在褪黑素的节律性已经被几个体内和体外研究证明，但它在这个组织中的合成和调节的许多方面仍然不清楚。本研究的目标是确定合成褪黑素的细胞类型(S)，并阐明环境光和生物钟在调节哺乳动物视网膜褪黑素合成中的作用。第一个特定的目标将检验这样的假设，即视锥感光细胞含有褪黑素合成机制以及调节褪黑激素的生物钟组件。第二个目标将检验这一假设，即视杆状感光细胞和/或视网膜内神经元含有生物钟(S)，该生物钟驱动视锥细胞中视网膜褪黑素的生物合成。最后，第三个目标将检验这一假设，即锥形感光颜料在夜间暴露于光下后对视网膜褪黑素的抑制起到中介作用。在我们的研究中，我们将使用一系列新的和技术先进的技术，如双原位杂交、实时定量聚合酶链式反应和激光捕获解剖显微镜。视网膜褪黑素参与了视网膜生理的多个方面的调节；因此，了解这种激素(神经调节剂)是如何调节的，可能会提高我们对视网膜生理和病理的理解。现代生活方式已经极大地改变了我们每天暴露在光明和黑暗中，因此了解这种暴露对机体，特别是视网膜功能的影响是很重要的。

DESCRIPTION (provided by applicant): The presence of melatonin rhythmicity in the retina of mammals has been demonstrated by several in vivo and in vitro studies, but many aspects of its synthesis and regulation in this tissue are still obscure. The goals of the present research proposal are to identify the cell type(s) that synthesizes melatonin and to elucidate the role of environmental light and of the circadian clock in regulating melatonin synthesis in the retina of mammals. The first specific aim will test the hypothesis that cone photoreceptors contain the melatonin synthesizing machinery as well as the circadian clock components to regulate it. The second aim will test the hypothesis that rod photoreceptors and/or inner retinal neurons contain the circadian clock(s) that drives retinal melatonin biosynthesis in cones. Finally, the third aim will test the hypothesis that cone photopigments mediate the suppression of retinal melatonin that follows exposure nocturnal exposure to light. In our research we will use a wide array of new and technologically advanced techniques such as dual in situ hybridization, quantitative real time PCR and Laser Capture Dissecting Microscopy. Retinal melatonin is involved in the modulation of several aspects of retinal physiology; thus the understanding of how this hormone (neuromodulator) is regulated will likely improve our understanding of retinal physiology and pathologies. Modem life style has tremendously changed our daily exposure to light and darkness and thus it is important to understand the effect that such exposure may have on the organism and, in particular, retinal function.