Expression profile of peripheral immune cells-derived coding and long non-coding RNAs in patients with proliferative vitreoretinopathy. Expression profile of peripheral immune cells-derived coding and long non-coding RNAs in patients with proliferative vitreoretinopathy

Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods: In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells (PBMCs) from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Ingenuity Pathway Analysis (IPA) were employed to classify the function of these differentially expressed genes (DEGs). Results: Compared to the controls, there were 319 genes upregulated, and 191 genes downregulated in PVR patients. GO, and KEGG enrichment analyses as well as IPA showed that these upregulated genes were significantly enriched in immune-related and infection-relate terms. Immune-related gene NFKBIA, CXCL2, and CXCL8 were detected as hub-genes in the co-expression network, while lncRNAs such as AC007032.1, AC037198.2, AL929472.2, and SLED1 were highly co-expressed with them. lncRNA-mRNA interactions analysis also showed that putative targeted genes of these differentially expressed lncRNAs were also significantly enriched in immune-related or infection-relate pathways. Conclusion: Our study highlights the transformation of immune-related genes/pathways in PVR by comparing controls, and validates several critical genes and lncRNAs, which are serving as potential diagnostic markers for PVR patients. Overall design: peripheral blood mononuclear cells mRNA profiles of proliferative vitreoretinopathy patients and idiopathic epiretinal membrane patients.

外周免疫应答（peripheral immune response）已被证实对增生性玻璃体视网膜病变（proliferative vitreoretinopathy, PVR）发挥关键作用。然而，可作为PVR预后指标或治疗靶点的可靠免疫相关因子仍有待进一步探索。方法：本研究通过全转录组测序（whole-transcriptome sequencing）对增生性玻璃体视网膜病变患者的外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）进行转录组分析，并对外周免疫细胞中的长链非编码RNA-信使RNA（lncRNA-mRNA）互作进行分析，以探索可能介导PVR免疫病理及继发视网膜损伤的通路。本研究采用基因本体（Gene Ontology, GO）富集分析、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析以及IPA通路分析（Ingenuity Pathway Analysis, IPA），对上述差异表达基因（differentially expressed genes, DEGs）的功能进行注释分类。结果：与对照组相比，PVR患者外周血单个核细胞中共有319个基因上调、191个基因下调。GO、KEGG富集分析及IPA结果显示，上述上调基因显著富集于免疫相关及感染相关功能条目。免疫相关基因NFKBIA、CXCL2及CXCL8被鉴定为共表达网络中的枢纽基因，而AC007032.1、AC037198.2、AL929472.2及SLED1等长链非编码RNA与这些枢纽基因存在高度共表达关系。长链非编码RNA-信使RNA互作分析还显示，这些差异表达长链非编码RNA的潜在靶基因同样显著富集于免疫相关或感染相关通路。结论：本研究通过对比对照组与PVR患者样本，揭示了PVR中免疫相关基因及通路的表达变化，并验证了数个可作为PVR患者潜在诊断标志物的关键基因与长链非编码RNA。实验设计：对增生性玻璃体视网膜病变患者及特发性黄斑前膜患者的外周血单个核细胞进行信使RNA（mRNA）表达谱分析。