Regulation of optic stalk development by microglia

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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.