Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA; Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, USA.
Bascom Palmer Eye Institute, University of Miami, Miami, FL, USA; Miami Integrative Metabolomics Research Center, University of Miami, Miami, FL, USA; Case Western Reserve University, Cleveland, OH, USA.
Exp Eye Res. 2020 May;194:108024. doi: 10.1016/j.exer.2020.108024. Epub 2020 Apr 1.
We report an analysis of the aqueous humor (AH) metabolome of primary open angle glaucoma (POAG) in comparison to normal controls. The AH samples were obtained from human donors [control (n = 35), POAG (n = 23)]. The AH samples were subjected to one-dimensional H nuclear magnetic resonance (NMR) analyses on a Bruker Avance 600 MHz instrument with a 1.7 mM NMR probe. The same samples were then subjected to isotopic ratio outlier analysis (IROA) using a Q Exactive orbitrap mass spectrometer after chromatography on an Accela 600 HPLC. Clusterfinder Build 3.1.10 was used for identification and quantification based on long-term metabolite matrix standards. In total, 278 metabolites were identified in control samples and 273 in POAG AH. The metabolites identified were fed into previously reported proteome and genome information and the OmicsNet interaction network generator to construct a protein-metabolite interactions network with an embedded protein-protein network. Significant differences in metabolite composition in POAG compared to controls were identified indicating potential protein/gene pathways associated with these metabolites. These results will expand our previous understanding of the impeded AH metabolite composition, provide new insight into the regulation of AH outflow, and likely aid in future AH and trabecular meshwork multi-omics network analyses.
我们报告了原发性开角型青光眼（POAG）与正常对照相比的房水代谢组分析。房水样本取自人类供体[对照（n=35），POAG（n=23）]。房水样本在 Bruker Avance 600 MHz 仪器上进行一维 H 核磁共振（NMR）分析，使用 1.7 mM NMR 探头。然后，相同的样本在 Accela 600 HPLC 上进行色谱分离后，使用 Q Exactive 轨道阱质谱仪进行同位素比异常分析（IROA）。Clusterfinder Build 3.1.10 用于基于长期代谢物矩阵标准进行鉴定和定量。在对照样本中鉴定出 278 种代谢物，在 POAG AH 中鉴定出 273 种代谢物。鉴定出的代谢物被输入到先前报道的蛋白质组和基因组信息以及 OmicsNet 相互作用网络生成器中，以构建具有嵌入式蛋白质-蛋白质网络的蛋白质-代谢物相互作用网络。与对照相比，POAG 中代谢物组成的显著差异表明与这些代谢物相关的潜在蛋白质/基因途径。这些结果将扩展我们对受阻碍的 AH 代谢物组成的先前理解，为 AH 流出的调节提供新的见解，并可能有助于未来的 AH 和小梁网多组学网络分析。
