title: Retinal Ganglion Cell Loss is Delayed Following Optic Nerve Crush in NLRP3 Knockout Mice.
abstract: The NLRP3 inflammasome, a sensor for a variety of pathogen- and host-derived threats, consists of the adaptor ASC (Apoptosis-associated Speck-like protein containing a Caspase Activation and Recruitment Domain (CARD)), pro-caspase-1, and NLRP3 (NOD-Like Receptor family Pyrin domain containing 3). NLRP3-induced neuroinflammation is implicated in the pathogenesis and progression of eye diseases, but it remains unclear whether activation of NLRP3 inflammasome contributes to retinal ganglion cell (RGC) death. Here we examined NLRP3-induced neuroinflammation and RGC survival following partial optic nerve crush (pONC) injury. We showed that NLRP3 was up-regulated in retinal microglial cells following pONC, propagating from the injury site to the optic nerve head and finally the entire retina within one day. Activation of NLRP3-ASC inflammasome led to the up-regulation of caspase-1 and a proinflammatory cytokine, interleukin-1β (IL-1β). In NLRP3 knockout mice, up-regulation of ASC, caspase-1, and IL-1β were all reduced, and, importantly, RGC and axon loss was substantially delayed following pONC injury. The average survival time of RGCs in NLRP3 knockout mice was about one week longer than for control animals. Taken together, our study demonstrated that ablating the NLRP3 gene significantly reduced neuroinflammation and delayed RGC loss after optic nerve crush injury.
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dong-chuan Road, Shanghai 200240, China.|Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois 60208, USA.|Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Puyang
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.|Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dong-chuan Road, Shanghai 200240, China.
authors.forename: Peiji
authors.initials: P
authors.lastname: Liang
authors.affiliation: Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Troy
authors.affiliation: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.|Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000235:genetics* / Q000473:pathology*; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020170:Caspase 1