A novel uveitis model induced by lipopolysaccharide in zebrafish

作者全名："Xiao, Xiao; Liu, Zhangluxi; Su, Guannan; Liu, Huan; Yin, Wenhui; Guan, Yuxuan; Jing, Shixiang; Du, Liping; Li, Fuzhen; Li, Na; Yang, Peizeng"

作者地址："[Xiao, Xiao; Liu, Huan; Yin, Wenhui; Guan, Yuxuan; Jing, Shixiang; Du, Liping; Li, Fuzhen; Li, Na; Yang, Peizeng] First Affiliated Hosp Zhengzhou Univ, Henan Prov Eye Hosp, Henan Int Joint Res Lab Ocular Immunol & Retinal I, Zhengzhou, Peoples R China; [Liu, Zhangluxi; Su, Guannan; Yang, Peizeng] First Affiliated Hosp Chongqing Med Univ, Chongqing Eye Inst, Chongqing Branch Municipal Div Natl Clin Res Ctr O, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China"

通信作者："Yang, PZ (通讯作者)，First Affiliated Hosp Zhengzhou Univ, Henan Prov Eye Hosp, Henan Int Joint Res Lab Ocular Immunol & Retinal I, Zhengzhou, Peoples R China.; Yang, PZ (通讯作者)，First Affiliated Hosp Chongqing Med Univ, Chongqing Eye Inst, Chongqing Branch Municipal Div Natl Clin Res Ctr O, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000898364300001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：uveitis; zebrafish; inflammation; innate immunity; disease model

摘要："ObjectiveEndotoxin-induced uveitis (EIU) is an important tool for human uveitis study. This study was designed to develop a novel EIU model in zebrafish. MethodsAn EIU model in zebrafish was induced by intravitreal lipopolysaccharide (LPS) injection and was assessed dynamically. Optical coherence tomography (OCT) was used to assess infiltrating cells in the vitreous body. The histological changes wereevaluated using HE staining and immune cells were measured by immunofluorescence. The retinal RNA Sequencing (RNA-Seq) was used to explore the transcriptional changes during inflammation. RNA-Seq data were analyzed using time-course sequencing data analysis (TCseq), ClueGO plugin in Cytoscape, and Gene Set Enrichment Analysis (GSEA) software. Flow cytometry and retinal flat mounts were used to dynamically quantify the immune cells. ResultsEIU was successfully induced in zebrafish following intravitreal LPS injection. Inflammation appeared at 4 hours post injection (hpi), reached its peak at 24 hpi, and then resolved at 72 hpi. Immunofluorescence confirmed that massive influx ofneutrophils into the iris and vitreous body, and activation of microglia as evidenced by ameboid-shaped appearance in the retina. Retinal RNA-seq during the EIU course identified four gene clusters with distinct expression characteristics related to Toll-likereceptor signaling pathway, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, and extracellular matrix (ECM)-receptor interaction, respectively. Prednisone immersion inhibited the inflammatory response of EIU in zebrafish, whichwas confirmed by decreased neutrophils detected in flow cytometry and retinal flat mounts. ConclusionsWe developed a novel EIU model in zebrafish, which may be particularly useful for gene-editing and high-throughput screening of new drugs for the prevention and treatment of uveitis."

基金机构：Major Program of Medical Science and Technology Project of Health Commission of Henan Province [SBGJ202101011]; Natural Science Foundation Major International (Regional) Joint Research Project [81720108009]; National Natural Science Foundation Key Program [82230032]; National Natural Science Foundation Project [81970792]; Medical Science and Technology Project of Health Commission of Henan Province [SBGJ2020003031]

基金资助正文："This work was supported by the Major Program of Medical Science and Technology Project of Health Commission of Henan Province (SBGJ202101011), the Natural Science Foundation Major International (Regional) Joint Research Project (81720108009), National Natural Science Foundation Key Program (82230032), and the National Natural Science Foundation Project (81970792), the Medical Science and Technology Project of Health Commission of Henan Province (SBGJ2020003031)."