Abstract
Purpose: :
To test whether retinal insult at adulthood, in a model of glutamate intoxication, awakens the quiescent retinal progenitor cells (RPC), and if so, whether infiltrating monocyte-derived macrophages affect progenitor cell renewal following retinal insult.
Methods: :
Adult mice, subjected to retinal insult in a model of Glutamate intoxication, were administrated intra-vitreously with the cell proliferation marker 5-bromo-2-deoxyuridine (BrdU). Proliferation of RPC and recruitment of distinct myeloid populations were analyzed by immunohistochemistry and flow-cytometry. Bone-marrow chimeras were used to characterize these myeloid populations and specifically to identify the infiltrating monocyte-derived macrophages. Depletion and augmentation of these infiltrating cells were performed in order to evaluate their contribution to RPC renewal following an insult.
Results: :
Glutamate intoxication stimulated proliferation of Pax6+ and SOX2+ RPC in the adult ciliary body and changed the relative contribution of distinct myeloid populations in the retina. Specifically, retinal insult resulted in the infiltration of CD11b+ /CX3CR1+/Gr1+ blood borne monocyte-derived macrophages to the damaged retinal ganglion cell layer. Enhanced accumulation of this monocytic population at the damaged area augmented RPC proliferation, while ablation of these cells resulted in a reduced renewal of RPC.
Conclusions: :
Retinal insult evokes proliferation of the dormant adult RPC and recruitment of distinct myeloid populations to the retina. Specifically, monocyte-derived macrophages infiltrate to the damaged retina following the insult and enhance progenitor cell renewal.
Keywords: immunomodulation/immunoregulation • proliferation • wound healing