The tissue damage caused by transient ischemic injury is an essential component of the pathogenesis of retinal ischemia, which mainly hinges on the degree and duration of interruption of the blood supply and the subsequent damage caused by tissue reperfusion. Some research indicated that the retinal injury induced by ischemia-reperfusion (I/R) was related to reperfusion time. In this study, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model group and at different reperfusion time (24h, 72h, and 7d) with the aid of whole transcriptome sequencing technology, and the trend changes in time-varying mRNA, lncRNA, circRNA were obtained by chronological analysis. Then, candidate circRNAs, lncRNAs, and mRNAs were obtained as the intersection of differentially expression genes and trend change genes. Importance scores of the genes selected the key genes whose expression changed with the increase of reperfusion time. Also, the characteristic differentially expressed genes specific to the reperfusion time were analyzed, key genes specific to reperfusion time were selected to show the change in biological process with the increase of reperfusion time. As a result, 316 candidate mRNAs, 137 candidate lncRNAs, and 31 candidate circRNAs were obtained by the intersection of differentially expressed mRNAs, lncRNAs, and circRNAs with trend mRNAs, trend lncRNAs and trend circRNAs, 5 key genes (Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa) were selected by importance scores of the genes. The result of GSEA showed that key genes were found to play vital roles in antigen processing and presentation, regulation of the actin cytoskeleton, and the ribosome. A network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 34 miRNAs and 48 lncRNAs, and 81 regulatory relationship axes, and a network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 9 miRNAs and 3 circRNAs (circRNA_10572, circRNA_03219, circRNA_11359) and 12 regulatory relationship axes were constructed, the subcellular location, transcription factors, signaling network, targeted drugs and relationship to eye diseases of key genes were predicted. 1370 characteristic differentially expressed mRNAs (spec_24h mRNA), 558 characteristic differentially expressed mRNAs (spec_72h mRNA), and 92 characteristic differentially expressed mRNAs (spec_7d mRNA) were found, and their key genes and regulation networks were analyzed. In summary, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model groups and at different reperfusion time (24h, 72h, and 7d). 5 key genes, Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa, were selected. Key genes specific to reperfusion time were selected to show the change in biological process with the increased reperfusion time. These results provided theoretical support and a reference basis for the clinical treatment.

中文翻译：

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大鼠视网膜缺血/再灌注损伤潜在关键基因的综合生物信息学分析

短暂性缺血损伤引起的组织损伤是视网膜缺血发病的重要组成部分，其主要取决于血供中断的程度和持续时间以及随后组织再灌注造成的损伤。有研究表明，缺血再灌注（I/R）引起的视网膜损伤与再灌注时间有关。本研究借助全转录组测序技术筛选了对照组和模型组之间以及不同再灌注时间（24h、72h和7d）差异表达的circRNA、lncRNA和mRNA，并分析了随时间的变化趋势。通过时间顺序分析获得不同的mRNA、lncRNA、circRNA。然后，获得候选circRNA、lncRNA和mRNA作为差异表达基因和趋势变化基因的交集。基因重要性评分选择表达随再灌注时间增加而变化的关键基因。同时对再灌注时间特异的特征性差异表达基因进行分析，筛选出再灌注时间特异的关键基因来显示随再灌注时间增加的生物学过程的变化。结果，通过差异表达的mRNA、lncRNA和circRNA与趋势mRNA、趋势lncRNA和趋势circRNA的交叉，获得316个候选mRNA、137个候选lncRNA和31个候选circRNA，5个关键基因(Cd74、RT1-Da、 RT1-CE5、RT1-Bb、RT1-DOa)根据基因的重要性评分进行选择。 GSEA的结果表明，关键基因在抗原加工和呈递、肌动蛋白细胞骨架和核糖体的调节中发挥着重要作用。一个网络包括4个关键基因（Cd74、RT1-Da、RT1-Bb、RT1-DOa）、34个miRNA和48个lncRNA以及81个调控关系轴，一个网络包括4个关键基因（Cd74、RT1-Da、RT1-构建了9个miRNA和3个circRNA（circRNA_10572、circRNA_03219、circRNA_11359）和12个调控关系轴，预测了关键基因的亚细胞定位、转录因子、信号网络、靶向药物以及与眼部疾病的关系。共发现1370个特征差异表达mRNA（spec_24h mRNA）、558个特征差异表达mRNA（spec_72h mRNA）和92个特征差异表达mRNA（spec_7d mRNA），并分析其关键基因和调控网络。总之，我们筛选了对照组和模型组之间以及不同再灌注时间（24h、72h和7d）差异表达的circRNA、lncRNA和mRNA。选择了5个关键基因：Cd74、RT1-Da、RT1-CE5、RT1-Bb、RT1-DOa。选择与再灌注时间相关的关键基因来显示随着再灌注时间的增加生物过程的变化。这些结果为临床治疗提供了理论支持和参考依据。