Tear metabolomics. An outstanding approach to the molecular diagnosis of glaucoma

Abstract

AbstractPurpose: The open‐angle glaucoma (OAG) is the first cause of irreversible blindness worldwide, being the main risk factor the elevated intraocular pressure (IOP). The molecular mechanisms of OAG development and progression remains incomplete. Because of this, biomarkers for early diagnosis of OAG are not conclusive. We deal with understanding the metabolomics of OAG by using 1H‐ nuclear magnetic resonance (NMR) spectroscopy in tear samples for searching specific metabolites that improve early molecular diagnosis of OAG.Methods: 1H NMR monodimensional experiments were acquired from tears in 30 tear samples (OAG patients: n = 11 and healthy controls: n = 19). Additionally, 2D (TOCSY and 1H‐13C HSQC) experiments were acquired in a reduced set of samples to assign the resonances. Spectra underwent phase, baseline and chemical shift correction. The signals in the spectra were assigned, integrated and normalized to the total sum of integrals. Finally, data were analysed by multivariate statistics (PLS‐DA) to determine a model to discriminate between the controls and OAG tears. The whole data set was split into calibration (18 samples) to calculate the model and validation set (10 samples) to test the performance and the ability for disease discrimination.Results: The calculated PLS‐DA model showed a sensitivity of 100% and a specificity of 83.3% to discriminate OAG patient's tears versus control tears in the validation set. The set of metabolites participating is this discriminant model were obtained, mainly those involved in specific cellular and molecular pathways regarding the pathologic mechanisms of OAG.Conclusions: Data obtained by 1H‐NMR spectroscopy in tears confirms the validity of metabolomics as a non‐invasive approach to better OAG managing.