外伤性视网膜增殖膜转录组分析

Transcriptomic analysis of traumatic proliferative membrane

背景眼外伤是导致视力丧失的重要原因。外伤性增殖性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)是导致伤眼不良预后的重要原因,其发病机制尚不清楚。目的通过对开放性眼外伤后不同时期PVR增殖膜(视网膜前膜和视网膜下膜)转录组测序(RNA-sequencing,RNA-seq)分析,探究不同时期参与损伤修复过程的差异表达基因(differentially expressed genes,DEGs)及信号通路的变化。方法本研究收集的北京大学第三医院眼科2015年1-12月4例男性(12~45岁)眼外伤患者标本,拟采用Bulk转录组测序技术检测开放性眼外伤后视网膜增殖膜的RNA表达,分析早期与晚期增殖膜内转录组差异基因的表达情况。结果通过京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析,发现晚期增殖膜细胞外基质受体相互作用、细胞因子-细胞因子受体相互作用、细胞黏附分子、蛋白质的消化和吸收通路被激活,对应的上调基因有ITGA8、TNFRSF4、CLDN5、COL3A1。结论整合素β8亚单位有可能在PVR增殖膜RPE细胞的转分化过程中起到重要的作用。在血-眼屏障修复过程中,ATP1A2、SLC8A3和SLC7A15P基因起到了重要作用。

Background Ocular trauma is an important cause of visual loss.Traumatic proliferative vitreoretinopathy(PVR)is an important cause of poor prognosis of ocular injury,and its mechanism remains unclear.Objective To find the differentially expressed genes(DEGs)involved in the process of injury repair and analyze the changes of signal pathways at different stages by sequencing the transcriptome of the PVR proliferative membrane(epiretinal membrane and subretinal membrane)in different periods after open globe injuries.Methods From January to December in 2015,4 male patients with age ranging from 12 to 45 years admitted to the Department of Ophthalmology,Peking University Third Hospital were included in this study.Their RNA expression of retinal proliferative membrane after open globe injury was detected by Bulk RNA seq technology.The expression of differential genes in early and late proliferative membrane transcriptome was analyzed.Results Through KEGG analysis,we found that ECM receptor interaction,cytokine receptor interaction,cell adhesion molecules,protein digestion and absorption pathways in late proliferative membrane were activated,and the corresponding up-regulated genes were ITGA8,TNFRSF4,CLDN5,and COL3A1.Conclusion Integrinsβ8 subunit may play an important role in the transdifferentiation of RPE cells in the PVR proliferative membrane.In addition,ATP1A2,SLC8A3 and SLC7A15P genes are of great significance in the repair of the blood-ocular barrier.