Deep mining of the molecular mechanisms underlying diabetic retinopathy (DR) is critical for the development of novel therapeutic targets. This study aimed to identify key molecular signatures involved in experimental DR on the basis of integrated bioinformatics analysis. Four datasets consisting of 37 retinal samples were downloaded from the National Center of Biotechnology Information Gene Expression Omnibus. After batch-effect adjustment, bioinformatics tools such as Networkanalyst, Enrichr, STRING, and Metascape were used to evaluate the differentially expressed genes (DEGs), perform enrichment analysis, and construct protein–protein interaction networks. The hub genes were identified using Cytoscape software. The DEGs of interest from the meta-analysis were confirmed by quantitative reverse transcription-polymerase chain reaction in diabetic rats and a high-glucose-treated retinal cell model, respectively. A total of 743 DEGs related to lens differentiation, insulin resistance, and high-density lipoprotein (HDL) cholesterol metabolism were obtained using the meta-analysis. Alterations of dynamic gene expression in the chloride ion channel, retinol metabolism, and fatty acid metabolism were involved in the course of DR in rats. Importantly, H3K27m3 modifications regulated the expression of most DEGs at the early stage of DR. Using an integrated bioinformatics approach, novel molecular signatures were obtained for different stages of DR progression, and the findings may represent distinct therapeutic strategies for DR patients.

中文翻译：

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实验性糖尿病视网膜病变发病机制中新的关键分子特征的鉴定


深入挖掘糖尿病视网膜病变（DR）的分子机制对于开发新的治疗靶点至关重要。本研究旨在基于综合生物信息学分析来识别实验 DR 中涉及的关键分子特征。从国家生物技术信息基因表达综合中心下载了由 37 个视网膜样本组成的四个数据集。经过批次效应调整后，利用Networkanalyst、Enrichr、STRING、Metascape等生物信息学工具对差异表达基因（DEG）进行评估，进行富集分析，构建蛋白质相互作用网络。使用 Cytoscape 软件识别中心基因。荟萃分析中感兴趣的 DEG 分别通过糖尿病大鼠和高血糖处理的视网膜细胞模型的定量逆转录聚合酶链反应得到证实。通过荟萃分析，总共获得了 743 个与晶状体分化、胰岛素抵抗和高密度脂蛋白 (HDL) 胆固醇代谢相关的 DEG。氯离子通道、视黄醇代谢和脂肪酸代谢动态基因表达的改变参与了大鼠DR的病程。重要的是，H3K27m3 修饰在 DR 早期调节大多数 DEG 的表达。利用综合生物信息学方法，获得了 DR 进展不同阶段的新分子特征，这些发现可能代表了 DR 患者的不同治疗策略。