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

视网膜时钟调节细胞活力、视网膜电路和运动活动节律

基本信息

批准号：
10612904
负责人：
Kenkichi Baba
金额：
$ 35.5万
依托单位：
MOREHOUSE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-17 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612904
关键词：
ARNTL gene Acceleration Affect Aging Antioxidants Behavior Behavior Control Bilateral Brain Brain-Derived Neurotrophic Factor Cell Death Cell Death Induction Cell Line Cell Survival Cell model Cells Cessation of life Circadian Dysregulation Circadian Rhythm Disorder Circadian Rhythms Circadian desynchrony Cone Couples Darkness Data Defect Dendrites Environment Excision Eye Enucleation Eye diseases Gene Expression Genes Genetic Glial Fibrillary Acidic Protein Goals Hamsters Jet Lag Syndrome Knockout Mice Life Lipids Metabolism Molecular Morphology Motor Activity Mus Neuronal Plasticity Ocular Pathology Organism Output Oxidative Stress Oxidative Stress Induction Pathology Periodicity Photoreceptors Physiology Population Process Reactive Oxygen Species Regulation Research Retina Retinal Cone Retinal Diseases Retinal Photoreceptors Role Series Signal Transduction Tamoxifen Techniques Technology Testing Transgenic Mice Vision Visual Work aged blind catalase circadian circadian pacemaker experimental study glutathione peroxidase insight molecular clock neural circuit neuronal circuitry oxidation peroxiredoxin real time monitoring response retinal neuron shift work suprachiasmatic nucleus

项目摘要

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.

实验证据表明，哺乳动物视网膜生理学和功能的许多方面都是不可或缺的。在视网膜生物钟的控制下。研究还表明，视网膜分子钟及其输出信号导致视网膜疾病和病理。Bmal1是生物钟的关键组成部分，分子生物钟机制我们以前的研究表明，Bmal1的去除，视网膜调节视网膜和视锥光感受器活力的神经回路。目前的目标是本研究旨在探讨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的。在具体目标1中，我们将使用661W细胞系研究视锥细胞活力的时钟调节机制。在具体目标2，我们确定是否环境昼夜节律中断（ECD，例如时差）影响视网膜功能和电路在具体目标3中，我们将检验以下假设：来自视网膜的bmal 1改变昼夜行为节律。在我们的研究中，我们将使用各种新的技术先进的技术以及几种转基因小鼠和细胞系将被利用我们的建议将提供重要的见解的作用，昼夜节律钟的调制视觉功能、光感受器活力和行为节律。