Transcriptional control of stress-induced resistance to retinal degeneration

应激诱导的视网膜变性抵抗力的转录控制

• 批准号: 10477262
• 负责人: John D Ash
• 金额: $ 37.22万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10477262
• 关键词: Affect; Age related macular degeneration; Binding; Blindness; Cell Death; Cells; Cessation of life; ChIP-seq; Cytoprotection; Data; Data Set; Disease; Disease Clusterings; FGF2 gene; Gene Expression; Gene Mutation; Genes; Genetic Transcription; Gliosis; Individual; Inflammation; Inflammatory; Injections; Injury; Knockout Mice; Knowledge; LIF gene; LIFR gene; Lead; Light; Mediating; Methods; Microglia; Modeling; Muller' s cell; Mus; Mutation; NF-kappa B; Pathologic; Persons; Photoreceptors; Phototransduction; Play; Publications; Publishing; Quality of life; Regulation; Research; Resistance; Retina; Retinal Degeneration; Rod; Role; Signal Transduction; Site; Stress; Techniques; Testing; Tissues; Transcription Coactivator; Transcriptional Activation; Transcriptional Regulation; Transducers; United States; Work; antagonist; biological adaptation to stress; cell type; cytokine; design; differential expression; inherited retinal degeneration; injured; novel therapeutics; promoter; receptor; response; retinal neuron; retinal rods; single-cell RNA sequencing; stress state; transcription factor

Abstract: Retinal degenerations are a large cluster of diseases characterized by the irreversible loss of photoreceptors. The death of these cells results in a permanent loss of vision that can have debilitating impacts on an individual's quality of life. Despite the diversity among triggers for retinal degenerations, the mechanisms surrounding photoreceptor death are often similar, suggesting the possibility of developing gene/mutation-independent approaches to reduce blindness from multiple forms of retinal degeneration. We and others have shown that STAT3 is activated in all retinal cells, including photoreceptors and Müller cells during inherited retinal degeneration. Additional work has shown that activation of STAT3 plays an essential role in promoting a wide array of gene expression changes to increase the cell’s capacity to resist cell death. However, despite these impressive findings, little progress has been made in identifying the mechanisms by which STAT3 regulates protection. In this project, we will use state of the art techniques including single-cell RNA-seq and integrating the data with cell-specific ChIP-seq to comprehensively identify all genes and transcriptional networks regulated by STAT3 in retinal Müller cells and rods.

文摘: