Affordable Access

deepdyve-link
Publisher Website

Involvement of the NLRC4 inflammasome in promoting retinal ganglion cell death in an acute glaucoma mouse model.

Authors
  • Yao, Ke1
  • Zhao, Yin1
  • Jin, Peiming1
  • Lou, Xiaotong1
  • Luo, Zhaoxia1
  • Zhang, Hong1
  • Li, Fei2
  • 1 Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. , (China)
  • 2 Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Experimental Eye Research
Publisher
Elsevier
Publication Date
Dec 15, 2020
Volume
203
Pages
108388–108388
Identifiers
DOI: 10.1016/j.exer.2020.108388
PMID: 33333046
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To explore the role of nucleotide-binding oligomerization domain-like receptors (NLRs) family caspase-activation and the recruitment domain containing 4 (NLRC4) inflammasome in retinal ganglion cell (RGC) injury induced by an acute glaucoma mouse model. A mouse model of acute ocular hypertension, which can lead to retinal ischemia-reperfusion (I/R) injury, was established. The expression level of NLRC4 was detected by polymerase chain reaction and western blotting. Localized expression of NLRC4 was detected by examining immunofluorescence in eyeball sections. Intravitreal adeno-associated virus 2(AAV2) administration was used to knockdown retinal Nlrc4. Fluoro-Gold labeled RGCs and TdT-mediated dUTP nick end labeling were used to evaluate the survival and apoptosis of RGCs. Tlr4-/- mice were utilized to explore whether NLRC4 inflammasome is influenced by Toll-like receptor4 (TLR4). NLRC4, expressed in RGCs and microglial cells, was actively involved in mouse retinal I/R injury. Knockdown of Nlrc4 using an AAV2 vector caused an obvious reduction in the generation of IL-1β led by the rapidly elevated intraocular pressure, and thereby improved the RGC survival. In addition, activation of the NLRC4 inflammasome could influence the phosphorylation of p38 and Jun N-terminal kinase, which was largely dependent on TLR4 signaling. Our study demonstrated the role of NLRC4 inflammasome in promoting RGC damage in mouse retinal I/R injury. Inhibition of NLRC4 might be leveraged as a potential therapeutic target in glaucomatous retinopathy. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Report this publication

Statistics

Seen <100 times