Abstract
Purpose: :
We recently showed that monocyte-derived macrophages take part in protecting retinal ganglion cells (RGCs) after glutamate-induced retinal insult, by locally exerting an immunoregulatory phenotype. In experimental autoimmune uveitis (EAU), macrophages are commonly associated with disease induction and progression. Appreciating the functional diversity of monocyte-derived macrophages, we set out to find whether the same subsets of monocyte-derived macrophages that are involved in homeostasis restoration following glutamate intoxication are also involved in protection against immune-mediated damage associated with EAU.
Methods: :
EAU was induced in male C57BL/6J mice by injection of human interphotoreceptor retinoid binding protein (IRBP)-derived peptide 1-20. The infiltration of monocyte-derived macrophages to the eye along disease course was monitored in CX3CR1-GFP bone marrow chimeric mice. Depletion experiments were performed in order to evaluate EAU resolution in the absence of monocyte-derived macrophages.
Results: :
EAU induction resulted in the appearance of a distinct myeloid population in the retina. Monocyte-derived macrophages infiltrated diseased retinas, and were absent from retinas of control mice. Inhibition of this infiltration at the resolution phase resulted in a decrease in FoxP3+ regulatory T cells, and affected the local cytokine milieu.
Conclusions: :
Monocyte-derived macrophages are active cells in EAU. These cells are present throughout disease course, affecting the local milieu in terms of cytokines and accumulation of other immune cells, and may play a role in disease resolution that is apparently distinct from their involvement in disease induction.
Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • neuroprotection