Regulation of optic stalk development by microglia

项目摘要 小胶质细胞是中枢神经系统的常驻神经免疫细胞，在发育过程中起着重要的作用。在早期的眼睛 视裂（OF）的发育、闭合以形成视柄对于正常视力是重要的，因为失败 这一过程的结果是缺损。OF的关闭依赖于局灶性细胞凋亡和基底的重塑 膜，虽然涉及的机制和细胞群体还没有完全确定。在关闭期间，我们 发现小胶质细胞集中在裂隙中，似乎是吞噬细胞。以确定是否 小胶质细胞参与OF闭合，第一个目的将确定小胶质细胞是否消除OF中的凋亡细胞。 的，并确定这是如何影响小胶质细胞重塑特性。第二个目标将测试一个 吞噬凋亡细胞消除所需的特异性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。这项研究将阐明小胶质细胞如何影响组织 重塑眼发育，并可能最终告知我们的理解是否小胶质细胞 有助于眼部疾病过程，例如导致视力丧失的缺损。

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.