The retinal clock modulates cell viability, retinal circuitry and locomotor activity rhythm

实验证据表明，哺乳动物视网膜的许多方面的生理和功能 在视网膜生物钟的控制下。研究还表明视网膜分子钟和它的 输出信号有助于视网膜疾病和病理。BMal1是昼夜节律的重要组成部分 分子生物钟机制。我们之前的研究表明，从 视网膜调节视网膜的神经回路和视锥感光细胞的活性。当前的目标是 建议研究视网膜生物钟在视网膜功能和SCN中的作用 昼夜节律组织。本申请包括三个具体目标。在具体目标1中，我们 将使用661W细胞系来研究锥体存活的时钟调节机制。在……里面 具体目标2，我们确定环境昼夜节律中断(ECD，例如时差) 会影响视网膜的功能和回路。在具体目标3中，我们将检验这样的假设：移除 来自视网膜的BMal1改变了昼夜行为节律。在我们的研究中，我们将使用广泛的新技术 和技术先进的技术以及几个转基因小鼠和细胞系将 被利用。我们的建议将为生物钟在调制中的作用提供重要的见解 视觉功能、光感受器活性和行为节律。

Experimental evidences indicate that many aspects of mammalian retinal physiology and function are under the control of a retinal circadian clock. Studies also indicate the retinal molecular clock and its output signals contribute to retinal disease and pathology. Bmal1 is a key component of the circadian molecular circadian clock mechanism. Our previous studies indicate that the removal of Bmal1 from retina modulates neural circuitry of retina and cone photoreceptors viability. The goal of the present proposal is to investigate the role of retinal circadian clock in retinal function and SCN circadian organization. The present application comprises three specific aims. In specific aim 1, we will investigate the mechanism underlying clock regulation of cone viability using 661W cell line. In specific aim 2, we determine whether the environmental circadian disruption (ECD, e.g. jet lag) affects retinal function and circuitry. In specific aim 3, we will test the hypothesis that the removal of Bmal1 from retina alters circadian behavior rhythm. In our research, we will use a wide array of new and technologically advanced techniques as well as several lines of transgenic mice and cell line will be used. Our proposal will provide important insights into the role of circadian clock in the modulation of visual function, photoreceptors viability and behavior rhythm.