Regulation of optic stalk development by microglia

小胶质细胞对视柄发育的调节

• 批准号: 10740772
• 负责人: Monica L Vetter
• 金额: $ 42.35万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740772
• 关键词: Ablation; Address; Apoptosis; Apoptotic; BAX gene; Basement membrane; Blindness; Brain; CSF1R gene; Cell Communication; Cell Death; Cell Shape; Cells; Chick; Coloboma; Congenital Disorders; Development; Diphtheria Toxin; Embryo; Event; Eye Development; Eye diseases; Failure; Gene Expression; Gene Expression Profile; Genes; Human; ITGAM gene; In Situ Hybridization; Knockout Mice; Mediating; Microarray Analysis; Microglia; Modeling; Morphogenesis; Mus; Nervous System; Neuroimmune; Optic Nerve; Optic vesicle; Optics; Pathway interactions; Phagocytes; Phenotype; Play; Population; Process; Property; Reaction; Regulation; Retina; Role; Shapes; Syndrome; Testing; Tissues; Vision; Visual impairment; early embryonic stage; experimental study; inhibitor; insight; nervous system development; optic stalk; postnatal; pregnant; recruit; selective expression

PROJECT SUMMARY Microglia, the resident neuroimmune cells of the CNS, play important developmental roles. During early eye development, closure of the optic fissure (OF) to form the optic stalk is important for normal vision, since failure of this process results in coloboma. OF closure depends upon focal apoptosis and remodeling of the basement membrane, although the mechanisms and cell populations involved are not fully defined. During OF closure we found that microglia are concentrated in the fissure and appear to be phagocytic. To determine whether microglia participate in OF closure, the first aim will determine whether microglia eliminate apoptotic cells in the OF, and determine how this influences microglia remodeling properties. The second aim will test the effect of a specific microglial recognition pathway required for phagocytic apoptotic cell elimination, and will then test the effect of microglia depletion on OF closure. This study will shed light on how microglia influence tissue remodeling in ocular development, and may ultimately inform our understanding of whether microglia contribute to ocular disease processes such as coloboma resulting in loss of vision.

项目总结