Myopia is a global health and economic issue. Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of many ocular diseases. We first evaluated the circRNA profiles and possible roles in vitreous humor samples of individuals with high myopia by a competitive endogenous RNA (ceRNA) array. Vitreous humor samples were collected from 15 high myopic (5 for ceRNA array, and 10 for qPCR) and 15 control eyes (5 for ceRNA array, and 10 for qPCR) with idiopathic epiretinal membrane (ERM) and macular hole (MH). 486 circRNAs (339 upregulated and 147 downregulated) and 264 mRNAs (202 upregulated and 62 downregulated) were differentially expressed between the high myopia and control groups. The expression of hsa_circ_0033079 (hsa-circDicer1), hsa_circ_0029989 (hsa-circNbea), hsa_circ_0019072 (hsa-circPank1) and hsa_circ_0089716 (hsa-circEhmt1) were validated by qPCR. Pearson analysis and multivariate regression analysis showed positive and significant correlations for axial length with hsa-circNbea and hsa-circPank1. KEGG analysis showed that the target genes of circRNAs were enriched in the mTOR, insulin, cAMP, and VEGF signaling pathways. GO analysis indicated that circRNAs mainly targeted transcription, cytoplasm, and protein binding. CircRNA-associated ceRNA network analysis and PPI network analysis identified several critical genes for myopia. The expression of circNbea, circPank1, miR-145-5p, miR-204-5p, , were validated by qPCR in the sclera of form-deprivation myopia (FDM) mice model. CircPank1miR-145-5p/ and circNbea/miR-204-5p/ were identified and may be important in the progression of myopia. Our findings suggest that circRNAs may contribute to the pathogenesis of myopia and may serve as potential biomarkers.

中文翻译：

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高度近视患者玻璃体液中的 CircRNA 表达谱和调控网络

近视是一个全球性的健康和经济问题。环状RNA（circRNA）已被证明在许多眼部疾病的发病机制中发挥重要作用。我们首先通过竞争性内源性 RNA (ceRNA) 阵列评估了高度近视个体玻璃体液样本中的 circRNA 图谱和可能的作用。玻璃体样本采集自 15 只高度近视眼（5 只用于 ceRNA 阵列，10 只用于 qPCR）和 15 只患有特发性视网膜前膜（ERM）和黄斑裂孔（MH）的对照眼（5 只用于 ceRNA 阵列，10 只用于 qPCR）。高度近视组和对照组之间有 486 个 circRNA（339 个上调，147 个下调）和 264 个 mRNA（202 个上调，62 个下调）表达差异。通过 qPCR 验证 hsa_circ_0033079 (hsa-circDicer1)、hsa_circ_0029989 (hsa-circNbea)、hsa_circ_0019072 (hsa-circPank1) 和 hsa_circ_0089716 (hsa-circEhmt1) 的表达。 Pearson 分析和多元回归分析显示眼轴长度与 hsa-circNbea 和 hsa-circPank1 呈显着正相关。 KEGG分析显示，circRNA的靶基因富集于mTOR、胰岛素、cAMP、VEGF信号通路。 GO分析表明circRNA主要靶向转录、细胞质和蛋白质结合。 CircRNA相关的ceRNA网络分析和PPI网络分析确定了几个近视的关键基因。通过 qPCR 在形觉剥夺性近视 (FDM) 小鼠模型巩膜中验证 circNbea、circPank1、miR-145-5p、miR-204-5p 的表达。 CircPank1miR-145-5p/ 和 circNbea/miR-204-5p/ 已被鉴定，并且可能在近视的进展中发挥重要作用。我们的研究结果表明，circRNA 可能有助于近视的发病机制，并可作为潜在的生物标志物。