Photic and circadian regulation of retinal melatonin.

描述（由申请人提供）：哺乳动物视网膜中褪黑激素节律性的存在已被一些体内和体外研究证明，但其在该组织中的合成和调节的许多方面仍然不清楚。本研究计划的目标是确定合成褪黑激素的细胞类型，并阐明环境光和生物钟在调节哺乳动物视网膜中褪黑激素合成中的作用。第一个具体目标是测试锥体光感受器包含褪黑激素合成机制以及生物钟成分来调节它的假设。第二个目标将测试一个假设，即视杆光感受器和/或视网膜内神经元包含驱动视锥细胞视网膜褪黑激素生物合成的生物钟。最后，第三个目标将测试假设，视锥光色素介导视网膜褪黑素的抑制，暴露在夜间暴露于光。在我们的研究中，我们将使用广泛的新技术和先进的技术，如双原位杂交，定量实时PCR和激光捕获解剖显微镜。视网膜褪黑素参与视网膜生理的几个方面的调节；因此，了解这种激素（神经调节剂）是如何被调节的，可能会提高我们对视网膜生理学和病理学的理解。现代生活方式极大地改变了我们每天接触光和黑暗的方式，因此了解这种接触可能对生物体，特别是视网膜功能产生的影响是很重要的。

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.