Role of CX3CR1 in the Mobilization of Phagocytic Retinal Microglial Cells

Abstract

Purpose: : We recently showed that retinal CX3CR1-dependent microglial cells (MC) accumulation may be a novel pathogenic pathway leading to age-related macular degeneration. However, the reason for subretinal MC accumulation and their fate after having engulfed retinal debris is poorly understood.

Methods: : Electron microscopy and Immunohistochemistry of MC markers and antirhodopsin Ab on bright light exposed CX3CR1 KO and WT mice and RCS rats and controls.

Results: : In our bright-light exposure model, MCs accumulate in the subretinal space in CX3CR1-deficient mice more than in control mice. In addition, this bright-light insult was followed by photoreceptor degeneration. In a model of dystrophic Royal College of Surgeon (RCS) rats, MC containing rhodopsin or rod outer segments (ROS) were found outside the photoreceptor cell layer in the choroidal vasculature and inner retina suggesting egress from the subretinal space.

Conclusions: : Taken together, our data suggests that MC migrated to the subretinal space in a CX3CR1-independent way. However,the presence of rhodopsin-positive MC outside the photoreceptor cell layer in a retinal degeneration model suggests that subretinal MC egress from the photoreceptor cell layer. This mecanism might be altered in CX3CR1 deficient animals and lead to the observed subretinal MC accumulation.

Keywords: retinal degenerations: cell biology • age-related macular degeneration • microglia