Y U Peng1, Qiu Yiguo1, Lin Ru1, F U Xinyu1, Hao Bingtao2, Lei Bo1,3. 1. Department of Ophthalmology, First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, China. 2. Institute of Cancer Research, Southern Medical University, Guangzhou 510515, China. 3. Henan Provincial People's Hospital, Henan Eye Institute, Henan Eye Hospital, Zhengzhou 450003, China.
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 applicationof DEX (0.1%) eye drops every 4 h for 24 h. The anterior chamber inflammation was examined with a slit lamp and the clinicalscores were assessed. The morphological changes in the eyes were assessed at 24 h after LPS injection. The retinas wereharvested 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-timePCR. RESULTS: DEX alleviated the inflammatory response and reduced the mRNA expressions of IL-6, TNF- a, MCP-1 andICAM-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 GeneOntology (GO) terms was noted. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 6up-regulated and 2 down-regulated KEGG pathways. RIG-I-like receptor signaling pathway and several immune- andinflammation-related genes including Ifit1, H2-T24, Mx2 and Eif2ak2 were significantly down regulated by DEX. Verificationwith RT-PCR yielded results consistent with these findings. CONCLUSIONS: DEX alleviates LPS-induced inflammatory response inthe retina of mice, and such protective effect is probably mediated by RIG-I like receptor signal pathway and the immune-andinflammation-related genes.
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 applicationof DEX (0.1%) eye drops every 4 h for 24 h. The anterior chamber inflammation was examined with a slit lamp and the clinicalscores were assessed. The morphological changes in the eyes were assessed at 24 h after LPS injection. The retinas wereharvested 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-timePCR. RESULTS:DEX alleviated the inflammatory response and reduced the mRNA expressions of IL-6, TNF- a, MCP-1 andICAM-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 GeneOntology (GO) terms was noted. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed 6up-regulated and 2 down-regulated KEGG pathways. RIG-I-like receptor signaling pathway and several immune- andinflammation-related genes including Ifit1, H2-T24, Mx2 and Eif2ak2 were significantly down regulated by DEX. Verificationwith RT-PCR yielded results consistent with these findings. CONCLUSIONS:DEX alleviates LPS-induced inflammatory response inthe retina of mice, and such protective effect is probably mediated by RIG-I like receptor signal pathway and the immune-andinflammation-related genes.
Authors: M Ashburner; C A Ball; J A Blake; D Botstein; H Butler; J M Cherry; A P Davis; K Dolinski; S S Dwight; J T Eppig; M A Harris; D P Hill; L Issel-Tarver; A Kasarskis; S Lewis; J C Matese; J E Richardson; M Ringwald; G M Rubin; G Sherlock Journal: Nat Genet Date: 2000-05 Impact factor: 38.330