Microglia, the resident neuroimmune cells of the CNS, play important developmental roles. While brain microglia have been extensively studied, less is known about the molecular properties and function of microglia in the developing retina. The goal of this proposal is to address how retinal microglia change over the course of development, the molecular pathways involved and how this relates to their function.
The first aim will determine whether there are molecularly distinct subpopulations of microglia in embryonic and early postnatal retina.
The second aim will address the function of microglia in the early postnatal retina by utilizing knowledge about their gene expression signature and targeting them for depletion. Finally, in the last aim we will test how developmental events govern retinal microglia phenotype and function, and the molecular pathways involved. By determining how changes in microglial properties are regulated and contribute to development of the retina we will gain insight into fundamental mechanisms of retina development and microglial function. This may ultimately inform our understanding of how microglia are modulated and participate in degenerative disease processes resulting in loss of vision.
The architecture of the retina is established during development by the generation and maintenance of a balanced complement of retinal cell types, which can be disrupted in pathological situations, including retinal neurodegeneration. The role of immune cells, such as resident microglia, in the development and function of the retina is poorly understood. This study will investigate the molecular pathways governing the properties of developing retinal microglia, and how this influences development of the retina itself.
