Differentiation of soluble aqueous humor metabolites in primary open angle glaucoma and controls. (May 2020)

• Record Type: Journal Article
• Authors: Myer, Ciara; Perez, Jordan; Abdelrahman, Leila; Mendez, Roberto; Khattri, Ram B.; Junk, Anna K.; Bhattacharya, Sanjoy K.
• Is Part Of: Experimental eye research. Volume 194(2020)
• Publication Date: 2020-05
• Subjects: Glaucoma -- Metabolomics -- Aqueous humor -- IROA -- POAG -- NMR; AH Aqueous humor -- POAG Primary open angle glaucoma -- IROA Isotopic ratio outlier analysis -- CB Ciliary body -- TM Trabecular meshwork; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.108024
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: 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 1 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. Graphical abstract: Image 1 Highlights: We report the metabolites of control versus primary open angle glaucoma (POAG) aqueous humor (AH). We used 1 H nuclear magnetic resonance (NMR) and isotopic ratio outlier analysis (IROA) using a Q Exactive mass spectrometer. There were significant metabolite changes found in the POAG AH.