ORIGINAL ARTICLE Metabolomics in non-arteritic anterior ischemic optic neuropathy patients by liquid chromatography–quadrupole time-of-flight mass spectrometry Fernando Andrade • Alicia Sa ´nchez-Ortega • Marta Llarena • Sergio Pinar-Sueiro • Marta Galdo ´s • M. Aranzazu Goicolea • Ramo ´n J. Barrio • Luis Alda ´miz-Echevarrı ´a Received: 18 March 2014 / Accepted: 11 July 2014 Ó Springer Science+Business Media New York 2014 Abstract Non-Arteritic Anterior Ischemic Optic Neu- ropathy (NAION) is a rare ischemic disease that affects the optic nerve. Pathophysiology and mechanism of ischemia of NAION remain uncertain, so the aim of this work is to establish the first metabolic fingerprinting of patients with NAION to discover possible new biomarkers. Twenty-four patients, aged 39–85 years, diagnosed with NAION, after a sudden loss of vision, were recruited for the study. Plasma samples of patients and controls were fingerprinted with liquid chromatography coupled to quadrupole time-of- flight by electrospray ionization, and obtained data were filtered, aligned and statistically analysed to identify new biomarkers. The identity of compounds that were found to be significant in class separation was later confirmed by obtaining the characteristic MS/MS spectra and online databases. In general, biochemical and metabolic profiles between patients and controls did not show profound dif- ferences, but NAION patients presented disturbances in the phospholipid composition which lead to reduced plasma values of LysoPCs. Altered levels of other metabolites, such as L-Palmitoylcarnitine, have been detected and could be considered as potential biomarkers. Keywords Metabolomics Á Biomarkers Á Phosphatidylcholine Á Optic neuropathy Á Ischemia Á Liquid chromatography–mass spectrometry 1 Introduction Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) represents the most common disease with optic disc edema (Jung et al. 2011) although it is a multi-factorial ischaemic event that affects the optic nerve, the main predisposing condition is not usually an isolated throm- boembolic event, but a combination of nocturnal arterial low pressure with a critical transient reduction of the optic nerve prefusion (Hayreh 2009). Small vessel circulatory insufficiency of the optic nerve head is the most widely accepted pathophysiology of NAION, but the location of the associated vasculopathy and mechanism of ischemia remain uncertain. Patients with a small cup to disk ratio are predisposed to NAION and it is said to have a ‘‘disk at risk’’. Swelling within the confines of a tight disk may produce a ‘‘compartment syndrome’’, a vicious cycle of disk edema and peripapillary haemorrhages (Arnold 2003). In the Ischemic Optic Neuropathy Decompression Trial (IONDT) (IONDT Research Group 1995), 60 % of NAION patients had at least one vasculopathic risk factor, 47 % had hypertension, and 24 % had diabetes. Sleep apnea, generalized hypoperfusion, vasospasm, failure of autoregulation, severe anemia, and nocturnal hypotension are all potential, but unproven, contributory pathogenetic factors for NAION (Arnold 2003; Arnold and Levin 2002; Li et al. 2007). An underlying mitochondrial abnormality has also been suggested due to the relationship of mito- chondria with oxidative phosphorylation and apoptosis (Bosley et al. 2004). F. Andrade Á M. Llarena Á L. Alda ´miz-Echevarrı ´a (&) Division of Metabolism, Cruces University Hospital, 48903 Barakaldo, Bizkaia, Spain e-mail: luisjose.aldamiz-echevarazuara@osakidetza.net A. Sa ´nchez-Ortega Á M. A. Goicolea Á R. J. Barrio Department of Analytical Chemistry, Faculty of Pharmacy, University of the Basque Country, Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain S. Pinar-Sueiro Á M. Galdo ´s Department of Ophthalmology, Cruces University Hospital, 48903 Barakaldo, Bizkaia, Spain 123 Metabolomics DOI 10.1007/s11306-014-0710-6