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。早期眼科期间 在发育过程中，视裂（OF）闭合形成视柄对于正常视力很重要，因为视裂（OF）失败 这个过程的结果是缺损。 OF 闭合取决于局灶性细胞凋亡和基底重塑 膜，尽管所涉及的机制和细胞群尚未完全确定。在 OF 关闭期间，我们 发现小胶质细胞集中在裂隙中，并且似乎具有吞噬能力。判断是否 小胶质细胞参与 OF 闭合，​​第一个目标是确定小胶质细胞是否消除 OF 中的凋亡细胞 OF，并确定这如何影响小胶质细胞重塑特性。第二个目标将测试效果 吞噬细胞凋亡消除所需的特定小胶质细胞识别途径，然后将测试 小胶质细胞耗竭对 OF 闭合的影响。这项研究将揭示小胶质细胞如何影响组织 眼部发育中的重塑，并可能最终帮助我们了解小胶质细胞是否 导致眼部疾病过程，例如导致视力丧失的缺损。