Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. While microglia have been studied extensively in autoimmune uveitis, their exact function remains uncertain. The objective of the current study was to determine whether resident microglia are necessary and sufficient to initiate and amplify retinal inflammation in autoimmune uveitis. In this study, we clearly demonstrate that microglia are essential for initiating infiltration of immune cells utilizing a murine model of experimental autoimmune uveoretinitis (EAU) and the recently identified microglia-specific marker P2ry12. Initiating disease is the primary function of microglia in EAU, since eliminating microglia during the later stages of EAU had little effect, indicating that the function of circulating leukocytes is to amplify and sustain destructive inflammation once microglia have triggered disease. In the absence of microglia, uveitis does not develop, since leukocytes cannot gain entry through the blood-retinal barrier, illustrating that microglia play a critical role in regulating infiltration of inflammatory cells into the retina.
SignificancePhotoreceptor cell death resulting from retinal detachment (RD) causes significant visual loss. While the immune system is activated during RD, its role is still unclear. Microglia are resident immune cells in the retina and are thought to be either protective or deleterious in response to neuronal injury, suggesting context-dependent effects. Here, we demonstrate that microglia limit retinal damage during acute injury, since microglial ablation led to increased photoreceptor death. Microglial morphological–activation changes triggered their migration into injured tissue where they formed intimate connections with infiltrating immune cells and phagocytized injured photoreceptors. These findings provide insight into the microglial response and function during RD, indicating microglia promote photoreceptor survival during acute phase injury by removing potentially damaging cell debris.
Vascular endothelial growth factor and also angiogenin, IP-10, MCP-1, MIP-1β, and Mig may be related to the pathogenesis of age-related macular degeneration. Intravitreal bevacizumab injection increases inflammatory cytokine levels, suggesting the induction of an inflammatory process.
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