Monocytic involvement in the neuroinflammatory response after retinal injury

Abstract

Aims/Purpose: Inflammation and disease lead to the recruitment of blood monocyte‐derived macrophages (MDM) to the central nervous system. The role of MDMs following a neuroinflammatory process after a lesion remains elusive because MDMs that enter the neural parenchyma are difficult to distinguish from microglia. The aim of this study is to elucidate the response of recruited MDMs after selective retinal ganglion cell (RGC) injury.Methods: Unilateral complete intra‐orbital optic nerve (ON) crush was performed in adult C57BL/6J LysM‐GFP mice carrying the selective marker green fluorescent protein (GFP) in myeloid MDM but not microglia, 1 week after retrograde labelling of RGCs with the neuronal tracer hydroxystilbamidine (OHSt) from the superior colliculi. This injury model allows to investigate how the retinal mononuclear phagocytic system responds to a neurodegenerative process via the phagocytic activity of its main cellular components, resident microglia and recruited MDM, both in the injured retina and its contralateral uninjured fellow retina, at 5‐, 7‐ or 10‐days post‐lesion.Results: At all‐time points after injury, microglial phagocytic activity was statistically significant in the injured retina compared to the uninjured fellow retina. In comparison to naïve retinas, the number of MDMs increases significantly after injury in both injured and uninjured retinas. In injured retinas the increase is statistically higher. However, only a subset of the recruited MDMs shows phagocytic activity in the injured retinas 10 days after the lesion but not before. In contrast, the population of MDMs in the contralateral uninjured retina shows no signs of phagocytic activity after the lesion.Conclusions: In the injured retina, recruited MDMs show an initial quiescent stage, with no phagocytic activity compatible with a neuroprotective state, followed by a delayed phase with detrimental behaviour for RGC survival. In the uninjured fellow retinas however, MDMs retain a quiescent stage. It is tempting to suggest that following ON injury, recruited MDMs adopt an initial neuroprotective stage followed by a detrimental phagocytic activity in the injured retina, whereas in the uninjured retina MDMs remain in the initial stage.