Fractalkine Receptor Regulates Microglial Neurotoxicity in an Experimental Mouse Glaucoma Model

Neuroinflammation underlies a wide variety of pathological processes in the central nerve system (CNS). Although previous experimental and clinical studies indicate that activation of neuroinflammatory signaling occurs early in glaucoma, the mechanisms controlling microglia activation are still poorly defined. In the present study, we investigated the role of the chemokine receptor Cx3cr1 in microglia activation and retinal ganglion cell (RGC) death in an experimental mouse glaucoma model with transient elevation of intraocular pressure (IOP). We demonstrated that retinal microglia played a pathogenic role in RGC death. Conversely, pharmacological suppression of microglia activation by minocycline increased RGC survival. Moreover, we found that Cx3cr1 deficiency enhanced microglial neurotoxicity and subsequently induced more extensive RGC loss, suggesting that Cx3cr1 suppressed microglial activation under elevated IOP. Overall, these findings provided novel insight into the mechanisms by which Cx3cr1 modulated microglia activation under elevated IOP. Suppression of microglia activation might be a potential treatment for slowing down the course of the disease and for increasing RGC survival in glaucoma patients. GLIA 2014;62:1943-1954 Main Points Retinal microglia played a pathogenic role in RGC death in an experimental mouse glaucoma model with transient elevation of intraocular pressure (IOP); Pharmacological suppression of microglia activation increased RGC survival;Cx3cr1 suppressed microglial activation under elevated IOP.