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

• 批准号: 10028851
• 负责人: John D Ash
• 金额: $ 46.71万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10028851
• 关键词: 5' -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; 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

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.

摘要： 视网膜具有很高的代谢活性，视网膜退化与线粒体有关。 功能障碍、新陈代谢失调和毒性氧化损伤。然而，人们对此知之甚少。 在退化的视网膜中，新陈代谢在正常情况下维持或被失调。AMPK(AMP- 激活的蛋白激酶)是高代谢组织中代谢的关键调节器，是 调节光感受器的代谢，以及它在视网膜新陈代谢中的作用将在本文中进行严格的研究 建议的项目采用功能增益和功能损失两种方法。过氧化物酶体增殖物激活 受体γ-辅活化子-α(pGC-1α)和β(pGC-1β)是线粒体生物发生的关键调控因子。 单磷酸腺苷依赖激酶(AMPK)是PGC-1活性的重要调节因子。我们的目标是 本研究旨在探讨AMPK和PGC-1活性在视网膜光感受器中的作用。