Key immune regulators in retinal ischemia-reperfusion injury via RNA sequencing.

IF 1.8 4区 医学 Q2 OPHTHALMOLOGY
International journal of ophthalmology Pub Date : 2025-07-18 eCollection Date: 2025-01-01 DOI:10.18240/ijo.2025.07.06
Shan He, Cui-Ying Liu, Chang-Hong Ren, Ting-Ting Meng, Heng Zhao, Xu-Xiang Zhang
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引用次数: 0

Abstract

Aim: To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury (RIRI) to identify potential therapeutic targets.

Methods: In the bulk RNA-seq analysis, This study performed differential gene expression analysis, weighted gene co-expression network analysis, and protein-protein interaction network analysis to identify hub genes. QuanTIseq was used to determine the composition of infiltrating immune cells. Following the identification of hub genes, single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes. Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed. Finally, the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction (qRT-PCR) was validated.

Results: Bulk RNA-seq analysis identified Stat2, Irf7, Irgm1, Igtp, Parp9, Irgm2, Nlrc5, and Tap1 as hub genes, with strong correlations to immune cell infiltration. Single-cell RNA-seq analysis further revealed six immune cell clusters, showing Irf7 predominantly in microglia and Tap1 in dendritic cells (DCs). And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity. qRT-PCR validated the upregulation of these genes.

Conclusion: In the acute phase of RIRI, Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.

通过RNA测序研究视网膜缺血再灌注损伤中的关键免疫调节因子。
目的:探讨视网膜缺血再灌注损伤(RIRI)的免疫细胞浸润及分子机制,寻找潜在的治疗靶点。方法:在大量RNA-seq分析中,本研究通过差异基因表达分析、加权基因共表达网络分析和蛋白-蛋白相互作用网络分析来鉴定枢纽基因。采用QuanTIseq测定浸润免疫细胞的组成。在确定中枢基因后,采用单细胞RNA-seq分析来确定表达这些中枢基因的特定免疫细胞类型。进一步进行细胞间通讯分析,探索免疫细胞之间的信号通路和相互作用。最后,利用实时定量聚合酶链反应(qRT-PCR)验证这些关键免疫调节因子在体内的表达。结果:Bulk RNA-seq分析发现Stat2、Irf7、Irgm1、Igtp、Parp9、Irgm2、Nlrc5和Tap1是枢纽基因,与免疫细胞浸润有很强的相关性。单细胞RNA-seq分析进一步揭示了6个免疫细胞簇,显示Irf7主要存在于小胶质细胞中,Tap1主要存在于树突状细胞(dc)中。细胞间通讯分析表明,小胶质细胞和dc在协调免疫活动中发挥核心作用。qRT-PCR证实了这些基因的上调。结论:在RIRI急性期,Irf7和Tap1可能是减少炎症和促进神经功能恢复的潜在治疗靶点。
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来源期刊
CiteScore
2.50
自引率
7.10%
发文量
3141
审稿时长
4-8 weeks
期刊介绍: · International Journal of Ophthalmology-IJO (English edition) is a global ophthalmological scientific publication and a peer-reviewed open access periodical (ISSN 2222-3959 print, ISSN 2227-4898 online). This journal is sponsored by Chinese Medical Association Xi’an Branch and obtains guidance and support from WHO and ICO (International Council of Ophthalmology). It has been indexed in SCIE, PubMed, PubMed-Central, Chemical Abstracts, Scopus, EMBASE , and DOAJ. IJO JCR IF in 2017 is 1.166. IJO was established in 2008, with editorial office in Xi’an, China. It is a monthly publication. General Scientific Advisors include Prof. Hugh Taylor (President of ICO); Prof.Bruce Spivey (Immediate Past President of ICO); Prof.Mark Tso (Ex-Vice President of ICO) and Prof.Daiming Fan (Academician and Vice President, Chinese Academy of Engineering. International Scientific Advisors include Prof. Serge Resnikoff (WHO Senior Speciatist for Prevention of blindness), Prof. Chi-Chao Chan (National Eye Institute, USA) and Prof. Richard L Abbott (Ex-President of AAO/PAAO) et al. Honorary Editors-in-Chief: Prof. Li-Xin Xie(Academician of Chinese Academy of Engineering/Honorary President of Chinese Ophthalmological Society); Prof. Dennis Lam (President of APAO) and Prof. Xiao-Xin Li (Ex-President of Chinese Ophthalmological Society). Chief Editor: Prof. Xiu-Wen Hu (President of IJO Press). Editors-in-Chief: Prof. Yan-Nian Hui (Ex-Director, Eye Institute of Chinese PLA) and Prof. George Chiou (Founding chief editor of Journal of Ocular Pharmacology & Therapeutics). Associate Editors-in-Chief include: Prof. Ning-Li Wang (President Elect of APAO); Prof. Ke Yao (President of Chinese Ophthalmological Society) ; Prof.William Smiddy (Bascom Palmer Eye instituteUSA) ; Prof.Joel Schuman (President of Association of University Professors of Ophthalmology,USA); Prof.Yizhi Liu (Vice President of Chinese Ophtlalmology Society); Prof.Yu-Sheng Wang (Director of Eye Institute of Chinese PLA); Prof.Ling-Yun Cheng (Director of Ocular Pharmacology, Shiley Eye Center, USA). IJO accepts contributions in English from all over the world. It includes mainly original articles and review articles, both basic and clinical papers. Instruction is Welcome Contribution is Welcome Citation is Welcome Cooperation organization International Council of Ophthalmology(ICO), PubMed, PMC, American Academy of Ophthalmology, Asia-Pacific, Thomson Reuters, The Charlesworth Group, Crossref,Scopus,Publons, DOAJ etc.
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