Role of microglia during retinal neurogenesis

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DESCRIPTION (provided by applicant): Normal visual function depends upon the generation of a balanced complement of retinal cell types during development. Although much has been learned about retinal progenitor proliferation and differentiation, little is known about how this s modulated by microglia, which is the resident neuroimmune cell of the central nervous system (CNS). Microglia infiltrates the mouse retina at early stages of eye development and is present by e11.5 coincident with the onset of retinal neurogenesis. However, despite the prevalence of microglia at the earliest stages of neurogenesis and suggestive evidence for a role in cortical neurogenesis, we lack a detailed understanding of whether these cells regulate progenitor cell survival, proliferation or differentiation, particularly in the developing retina. Here we propose o define the pattern of microglia distribution, activation and gene expression changes during retinal development, first by imaging GFP labeled microglia at multiple stages, and then by generating a comprehensive molecular profile of microglia over developmental time. Next we will test whether inhibiting or eliminating microglia alters retinal progenitor proliferation, survval or differentiation. This study will provide a detailed investigation of microglia function during embryonic eye development, and will shed light on the role of neuro-immune interactions on visual system development.