Regulators of retinal metabolism in healthy and degenerating retinas

健康和退化视网膜中视网膜代谢的调节剂

基本信息

批准号：
10455542
负责人：
John D Ash
金额：
$ 44.03万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10455542
关键词：
5&apos -AMP-activated protein kinase Adenosine Monophosphate Affect Age Age related macular degeneration Aging Biogenesis Biological Assay Catalytic Domain Cell Nucleus Cells Data Data Analyses Defect Development Disease Functional disorder Gene Expression Genes Genetic Transcription Glucose Glutamate Metabolism Pathway Glutamine Goals Inherited Knockout Mice Label Light Link Macular degeneration Measures Mediating Metabolic Metabolic Pathway Metabolism Metformin Mitochondria Mitochondrial DNA Mus Mutation Nuclear PPAR gamma Pathway Analysis Pathway interactions Persons Pharmaceutical Preparations Phosphotransferases Photoreceptors Ploidies Publishing Research Retina Retinal Degeneration Retinal Photoreceptors Rod Role Testing Therapeutic Thinness Tissues United States age related cofactor design gain of function gene function in vivo inherited retinal degeneration loss of function metabolomics mitochondrial dysfunction mitochondrial metabolism oxidative damage repaired response retinal neuron single-cell RNA sequencing transcriptome sequencing uptake

项目摘要

Abstract: The retina has high metabolic activity, and retinal degenerations have been associated with mitochondrial dysfunction, dysregulation of metabolism, and toxic oxidative damage. However, little is known about how metabolism is maintained under normal conditions or is dysregulated in degenerating retinas. AMPK (AMP- activated protein kinase) is a key regulator of metabolism in highly metabolic tissues and is a candidate to regulate metabolism in photoreceptors, and its role in retinal metabolism will be rigorously studied in this proposed project using both gain-of-function and loss-of-function approaches. Peroxisome proliferator-activated receptor gamma coactivator-alpha (PGC-1α) and beta (PGC-1β) are key regulators of mitochondrial biogenesis. Adenosine monophosphate dependent kinase (AMPK) is an important regulator of PGC-1 activity. Our goal in this study is to determine the roles of AMPK and PGC-1 activity in retinal photoreceptors.

抽象的：视网膜具有高代谢活性，视网膜变性与线粒体相关然而，人们对其如何发生却知之甚少。新陈代谢在正常条件下得以维持，或者在退化的视网膜中失调（AMP-）。活化蛋白激酶）是高度代谢组织中代谢的关键调节因子，是调节光感受器的代谢，本研究将严格研究其在视网膜代谢中的作用拟议的项目使用功能获得和功能丧失方法。受体γ辅激活因子-α (PGC-1α) 和β (PGC-1β) 是线粒体生物发生的关键调节因子。单磷酸腺苷依赖性激酶 (AMPK) 是 PGC-1 活性的重要调节因子。本研究旨在确定 AMPK 和 PGC-1 活性在视网膜感光器中的作用。