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Invest Ophthalmol Vis Sci. 2020 Apr 9;61(4):24. doi: 10.1167/iovs.61.4.24.
To identify processes that contribute to corticosteroid-induced ocular hypertension and candidate target genes for treatment.
A systematic search identified five human microarray datasets investigating the effect of dexamethasone versus a control medium on trabecular meshwork (TM) tissue. After thorough quality control, samples of low quality were removed, and the datasets were integrated. Additionally, a bovine RNA-sequencing dataset allowed to investigate differences in gene expression profiling between cows with and without corticosteroid-induced ocular hypertension (responders vs. nonresponders). The obtained datasets were used as input for parallel pathway analyses. Significantly changed pathways were clustered into functional categories and the results were further investigated. A network visualizing the differences between the responders and nonresponders was created.
Seven functional pathway clusters were found to be significantly changed in TM cells exposed to dexamethasone versus a control medium and in TM cells of responders versus nonresponders: collagen, extracellular matrix, adhesion, WNT-signaling, inflammation, adipogenesis, and glucose metabolism. In addition, cell cycle and senescence were only significantly changed in responders versus nonresponders. The network of the differential gene expression between responders and nonresponders shows many connections between the identified processes via shared genes.
Nine functional pathway clusters synthesize the molecular response to dexamethasone exposure in TM cells and are likely to be involved in the pathogenesis of corticosteroid-induced ocular hypertension.
确定导致皮质类固醇诱导性眼压升高的过程和治疗的候选靶基因。
系统检索确定了五个研究地塞米松与对照培养基对小梁网（TM）组织影响的人类微阵列数据集。经过彻底的质量控制，去除低质量的样本，并对数据集进行整合。此外，牛 RNA 测序数据集允许研究有和没有皮质类固醇诱导性眼压升高（应答者与非应答者）的牛之间基因表达谱的差异。获得的数据集被用作平行途径分析的输入。显著改变的途径被聚类到功能类别中，并进一步研究结果。创建了一个可视化应答者和非应答者之间差异的网络。
在暴露于地塞米松与对照培养基的 TM 细胞和应答者与非应答者的 TM 细胞中，发现七个功能途径簇发生显著变化：胶原、细胞外基质、粘附、WNT 信号、炎症、脂肪生成和葡萄糖代谢。此外，细胞周期和衰老仅在应答者与非应答者之间发生显著变化。应答者和非应答者之间差异基因表达的网络显示，通过共享基因，许多过程之间存在联系。
九个功能途径簇综合了 TM 细胞对地塞米松暴露的分子反应，可能参与皮质类固醇诱导性眼压升高的发病机制。
