Aims

Corneal nerve fibers are derived from the ophthalmic division of the trigeminal ganglion (TG). Here, by sequencing of microRNAs (miRNAs) and messenger RNAs (mRNAs) from diabetic and normal TG tissues, we aimed to uncover potential miRNAs, mRNAs, and the network of their interactions involved in the pathogenesis of diabetic corneal neuropathy.

Main methods

We performed RNA sequencing to systematically screen out differentially expressed miRNAs and mRNAs in TG tissues from diabetic and normal mice. Functional enrichment analyses were performed to illustrate the biological functions of differentially expressed mRNAs (DEmRNAs). Following this, miRNA-mRNA regulatory networks were built by means of bioinformatics methods to suggest regulatory role for miRNAs in the pathogenesis of diabetic corneal neuropathy. Finally, the credibility of the sequencing-based results was validated using qRT-PCR.

Key findings

Sequencing analyses disclosed that 68 miRNAs and 114 mRNAs were differentially expressed in diabetic TG tissues compared with normal TG samples. The functional analyses showed that DEmRNAs participated in diabetes-related biological processes. After applying an optimized approach to predict miRNA–mRNA pairs, a miRNA-mRNA interacting network was inferred. Subsequently, the expression and correlation of miR-350-5p and Mup20, miR-592-5p and Angptl7 as well as miR-351-5p and Elovl6 were preliminarily validated.

Significance

Our study provides a systematic characterization of miRNA and mRNA expression in the TG during diabetic corneal neuropathy and will contribute to the development of clinical diagnostic and therapeutic strategies for diabetic corneal neuropathy.

中文翻译：

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综合分析参与糖尿病角膜神经病的差异表达的microRNA和mRNA。

目的

角膜神经纤维源自三叉神经节（TG）的眼科。在这里，通过对来自糖尿病和正常TG组织的microRNA（miRNA）和信使RNA（mRNA）进行测序，我们旨在揭示潜在的miRNA，mRNA及其与糖尿病角膜神经病发病机制有关的相互作用网络。

主要方法

我们进行了RNA测序，以系统筛选出糖尿病和正常小鼠TG组织中差异表达的miRNA和mRNA。进行功能富集分析以说明差异表达的mRNA（DEmRNA）的生物学功能。此后，通过生物信息学方法建立了miRNA-mRNA调控网络，以暗示miRNA在糖尿病性角膜神经病发病机理中的调控作用。最后，使用qRT-PCR验证了基于测序的结果的可信度。

主要发现

测序分析显示，与正常TG样品相比，在糖尿病TG组织中68个miRNA和114个mRNA差异表达。功能分析表明DEmRNA参与了糖尿病相关的生物学过程。应用优化的方法预测miRNA-mRNA对后，推断出miRNA-mRNA相互作用网络。随后，初步验证了miR-350-5p和Mup20，miR-592-5p和Angptl7以及miR-351-5p和Elovl6的表达和相关性。

意义

我们的研究提供了糖尿病性角膜神经病变期间TG中miRNA和mRNA表达的系统表征，并将有助于糖尿病性角膜神经病变的临床诊断和治疗策略的发展。