Developmental regulation of retinal microglia

视网膜小胶质细胞的发育调控

基本信息

批准号：
10179402
负责人：
Monica L Vetter
金额：
$ 36.98万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10179402
关键词：
ARHGEF5 gene Address Adult Age Apoptosis Apoptotic Architecture Axon BAX gene Blindness Blood Vessels Brain Cell Count Cell Death Cells Complement Complement Receptor Cues Data Degenerative Disorder Dependence Development Diphtheria Toxin Disease Embryo Event Flow Cytometry Gene Expression Gene Expression Profile Gene Proteins Generations Genes Goals Health Heterogeneity ITGAX gene Immune In Situ Hybridization Injury Knockout Mice Knowledge Macrophage-1 Antigen Maintenance Maps Mediating Microglia Molecular Mus Myelogenous Nerve Degeneration Neuroglia Neuroimmune Neurons Pathologic Pathway interactions Phagocytes Phenotype Play Process Property Reaction Regulation Resistance Retina Retinal Diseases Retinal Ganglion Cells Role Shapes Signal Pathway Signal Transduction Spatial Distribution Stress Synapses Testing Transgenic Mice Up-Regulation Variant cell type course development genetic signature insight lipid metabolism molecular phenotype myelination newborn neuron postnatal promoter single-cell RNA sequencing transcriptome sequencing

项目摘要

PROJECT SUMMARY Microglia, the resident neuroimmune cells of the CNS, play important developmental roles. While brain microglia have been extensively studied, less is known about the molecular properties and function of microglia in the developing retina. The goal of this proposal is to address how retinal microglia change over the course of development, the molecular pathways involved and how this relates to their function. The first aim will determine whether there are molecularly distinct subpopulations of microglia in embryonic and early postnatal retina. The second aim will address the function of microglia in the early postnatal retina by utilizing knowledge about their gene expression signature and targeting them for depletion. Finally, in the last aim we will test how developmental events govern retinal microglia phenotype and function, and the molecular pathways involved. By determining how changes in microglial properties are regulated and contribute to development of the retina we will gain insight into fundamental mechanisms of retina development and microglial function. This may ultimately inform our understanding of how microglia are modulated and participate in degenerative disease processes resulting in loss of vision.

项目概要小胶质细胞是中枢神经系统的常驻神经免疫细胞，发挥着重要的发育作用。当大脑小胶质细胞已被广泛研究，但人们对小胶质细胞的分子特性和功能知之甚少在发育中的视网膜中。该提案的目标是解决视网膜小胶质细胞在整个过程中如何变化。发育、所涉及的分子途径以及这与其功能的关系。第一个目标将确定胚胎和产后早期是否存在分子上不同的小胶质细胞亚群视网膜。第二个目标是利用知识来解决小胶质细胞在产后早期视网膜中的功能关于它们的基因表达特征并针对它们进行消除。最后，在最后一个目标中，我们将测试如何发育事件控制视网膜小胶质细胞的表型和功能以及所涉及的分子途径。通过确定小胶质细胞特性的变化如何被调节并促进视网膜的发育我们将深入了解视网膜发育和小胶质细胞功能的基本机制。这可能最终让我们了解小胶质细胞如何调节并参与退行性疾病导致视力丧失的过程。