title: Fractalkine receptor regulates microglial neurotoxicity in an experimental mouse glaucoma model.
abstract: 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.
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005901:Glaucoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007429:Intraocular Pressure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D015703:Antigens, CD; D000073883:CX3C Chemokine Receptor 1; D002135:Calcium-Binding Proteins; C471885:Cx3cr1 protein, mouse; D008840:Microfilament Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D014404:Tubulin; D049452:Green Fluorescent Proteins; D008911:Minocycline
keywords: Cx3cr1; intraocular pressure; microglia; retinal ganglion cells