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：
10405547
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/10405547
关键词：
ARNTL gene Affect Aging Antioxidants Behavior Behavior Control Bilateral Brain Brain-Derived Neurotrophic Factor Cell Death 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 Disease Environment Excision Eye Enucleation Gene Expression Genes Genetic Glial Fibrillary Acidic Protein Goals Hamsters Jet Lag Syndrome Knockout Mice Life Lipids Metabolism Molecular Morphology Motor Activity Mouse Cell Line Mus Neuronal Plasticity Organism Output Oxidative Stress Pathology Periodicity Photoreceptors Physiology Play Population Process Reactive Oxygen Species Regulation Research Retina Retinal Cone Retinal Diseases Retinal Photoreceptors Role Series Signal Transduction Tamoxifen Techniques Testing Transgenic Mice Vision Visual aged blind catalase circadian circadian pacemaker experimental study glutathione peroxidase insight molecular clock neural circuit neuronal circuitry oxidation peroxiredoxin real time monitoring response 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和功能的许多方面都受到影响。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 是昼夜节律的关键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细胞的活力。目前的目标提案是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，我们确定环境昼夜节律是否受到干扰（ECD，例如时差反应）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：视网膜中的 Bmal1 会改变昼夜节律。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以及几种转基因小鼠和细胞系将被使用。我们的提案将为了解生物钟在调节中的作用提供重要的见解视觉功能、光感受器活力和行为节律。