Retinal cell elimination by microglia

小胶质细胞消除视网膜细胞

基本信息

批准号：
10224941
负责人：
Monica L Vetter
金额：
$ 18.49万
依托单位：
UNIVERSITY OF UTAH
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：
2020-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224941
关键词：
Address Aging Astrocytes Attention Binding Blindness Brain CCRL2 gene Cell Count Cell Death Cell Survival Cells Cellular Stress Complement Complement 1q Complement Receptor Complex Development Disease Embryo Embryonic Development Family Felis catus Flow Cytometry Gene Expression Gene Expression Profile Immune In Situ In Situ Hybridization Injury Ischemic Stroke Label Light Link MAPK8 gene MERTK gene Macrophage-1 Antigen Mediating Microglia Molecular Monkeys Muller&apos s cell Mus Nervous system structure Neuroglia Neuroimmune Neurons Newborn Infant Oligodendroglia Pathway interactions Phagocytes Phagocytosis Phosphatidylserines Photoreceptors Play Process Rattus Reaction Receptor Protein-Tyrosine Kinases Retina Retinal Diseases Retinal Ganglion Cells Role Signal Transduction Stress Synapses System Testing Up-Regulation cell type conditional knockout in vivo inherited retinal degeneration insight member mutant neuron loss newborn neuron postnatal progenitor receptor retinal neuron retinal progenitor cell scaffold selective expression single-cell RNA sequencing stroke model transcriptome sequencing

项目摘要

PROJECT SUMMARY Microglia, the resident neuroimmune cells of the CNS, play important developmental roles. During embryonic development we showed that retinal microglia target a subset of viable newborn retinal ganglion cells (RGCs) for phagocytic elimination through a process that requires complement signaling. The embryonic retina is a simple system to address how microglia target non-apoptotic cells for phagocytosis, with important implications for the role of microglia in cell loss during injury and disease. To understand the mechanisms of retinal cell elimination, the first aim will address the role of complement expression and stress pathways in RGCs. The second aim will test specific microglial recognition pathways required for phagocytic retinal cell elimination, including RGCs and astrocytes. This study will shed light on how microglia influence developmental remodeling in the retina, and may ultimately inform our understanding of how microglia participate in retinal 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。胚胎时期我们发现视网膜小胶质细胞以存活的新生视网膜神经节细胞（RGC）子集为目标通过需要补体信号传导的过程进行吞噬消除。胚胎视网膜是解决小胶质细胞如何靶向非凋亡细胞进行吞噬的简单系统，具有重要意义研究小胶质细胞在损伤和疾病期间细胞损失中的作用。了解视网膜细胞的机制消除，第一个目标将解决补体表达和应激途径在 RGC 中的作用。这第二个目标将测试吞噬性视网膜细胞消除所需的特定小胶质细胞识别途径，包括 RGC 和星形胶质细胞。这项研究将揭示小胶质细胞如何影响发育视网膜重塑，并可能最终帮助我们了解小胶质细胞如何参与视网膜导致视力丧失的疾病过程。