Protective role of retinal microglia and the regulation of resident retinal myeloid cells by the surface protein CD200
Retinal microglia represent a highly complex population of resident myeloid cells. Function ranges from control of neuronal growth to clearance of cellular debris. Microglia are implicated in the pathogenesis of diseases such as Multiple Sclerosis and Alzheimer's. Microglia possess a distinct immunophenotype in response to inflammatory mediators IFNγ and LPS where MHC class II, CD86 and CD40 are up regulated, conferring a putative antigen presenting function, but there is an IL-10 dependent loss of co-accessory molecule expression, suggesting that microglia may modulate immune responses within the retina and maintain the specialised immunoregulatory environment normally present. Maintenance of this environment is further mediated via retinal CD200 expression. Results suggest that CD200:CD200 receptor engagement suppresses macrophage activation and inhibition of this exacerbates tissue destruction. This thesis examined the contribution of CD200 expression on maintaining immune regulation within the retina. Novel data is presented that shows expression of CD200 on retinal vascular endothelium and neurons. CD200-/- mice have increased numbers of retinal microglia which display normal morphology, but unlike resident CD200+/+ retinal microglia express constitutive NOS2. In CD200-/- mice, onset and severity of IRBP peptide 1-20 induced EAU is accelerated but overall tissue destruction is no greater than seen in CD200+/+ mice. Despite increased levels of apoptosis within the retina throughout the course of disease, myeloid cell infiltrate is greater in CD200-/- mice at all time points, while the level of NOS2 expression during height of disease is less in CD200-/- mice. CD200-depletion does not affect either T cell proliferation or APC function. Results indicate that retinal vascular CD200 expression regulates myeloid cell numbers in the retina and trafficking during inflammation and that CD200:CD200 receptor balance regulates retinal microglial activation.