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：
10406289
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/10406289
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 Disease associated microglia 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.

项目摘要小胶质细胞是中枢神经系统的常驻神经免疫性细胞，起着重要的发育作用。大脑小胶质细胞已经进行了广泛的研究，对小胶质细胞的分子特性和功能知之甚少在发展中的视网膜中。该提案的目的是解决视网膜小胶质细胞在整个过程中的变化开发，所涉及的分子途径以及与其功能的关系。第一个目标确定胚胎和早期产后的小胶质细胞的分子亚群视网膜。第二个目的将通过利用知识来解决早期产后视网膜中小胶质细胞的功能关于它们的基因表达特征并将其靶向耗尽。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表型和功能，以及所涉及的分子途径。通过确定如何调节小胶质细胞的变化并有助于视网膜的发展我们将深入了解视网膜发展和小胶质功能的基本机制。这可能最终了解我们对如何调节小胶质细胞并参与退行性疾病的理解过程导致视力丧失。