Retinal transcriptome profile in mice following dexamethasone treatment for endotoxin-induced uveitis
10.3969/j.issn.1673-4254.2018.08.01
- VernacularTitle:地塞米松对内毒素诱导的小鼠葡萄膜炎的治疗效果及转录组分析
- Author:
Peng YU
1
;
Yiguo QIU
;
Ru LIN
;
Xinyu FU
;
Bingtao HAO
;
Bo LEI
Author Information
1. 重庆医科大学附属第一医院眼科//眼科学重庆市市级重点实验室//重庆市眼科研究所
- Keywords:
endotoxin-induced uveitis;
dexamethasone;
transcriptome;
RIG-I-like receptor signaling pathway;
inflammation
- From:
Journal of Southern Medical University
2018;38(8):901-909
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the changes in retinal transcriptome profile of mice with endotoxin-induced uveitis (EIU) following dexamethasone (DEX) treatment and explore the mechanisms underlying the therapeutic effect of DEX.Methods EIU was induced in BALB/c mice by intravitreal injection of 125 ng lipopolysaccharide (LPS),followed by topical application of DEX (0.1％) eye drops every 4 h for 24 h.The anterior chamber inflammation was examined with a slit lamp and the clinical scores were assessed.The morphological changes in the eyes were assessed at 24 h after LPS injection.The retinas were harvested for analysis of transcriptome profile using the next-generation sequencing (NGS)-based RNA sequencing (RNA-seq),and the expressions of the inflammatory cytokines and the differentially expressed genes (DEGs) were verified using real-time PCR.Results DEX alleviated the inflammatory response and reduced the mRNA expressions of IL-6,TNF-α,MCP-1 and ICAM-1 at 24 h after LPS injection.A total of 52 DEGs were identified by RNA-seq.Within these DEGs,37 genes were upregulated and 15 genes were down-regulated in LPS group as compared with DEX+LPS group.No significantly enriched Gene Ontology (GO) terms was noted.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 6 up-regulated and 2 down-regulated KEGG pathways.RIG-I-like receptor signaling pathway and several immune-and inflammation-related genes including Ifit1,H2-T24,Mx2 and Eif2ak2 were significantly down regulated by DEX.Verification with RT-PCR yielded results consistent with these findings.Conclusion DEX alleviates LPS-induced inflammatory response in the retina of mice,and such protective effect is probably mediated by RIG-I like receptor signal pathway and the immune-and inflammation-related genes.
