Abstract
PurposeSuperior limbic keratoconjunctivitis (SLK) is a bilateral, chronic inflammatory disease that recurs for up to several years; however, the fundamental processes involved in its pathogenic mechanisms remain unknown. We aimed to investigate the metabolomic alterations in the tear fluids of patients with superior limbic keratoconjunctivitis (SLK) compared with those of healthy volunteers (Ctrl group).MethodsWe performed a cross-sectional study involving 42 subjects. Tear fluid was taken from one eye of 24 SLK patients (40.13 ± 14.55 years, 83.33% female) and 18 healthy volunteers (Ctrl, 39.89 ± 9.2 years, 72.22% female) using Schirmer strips. After the liquid extraction of tear metabolites, samples were infused into the QE HFX Orbitrap mass spectrometer in both positive and negative ion mode. Metabolites were quantitatively analyzed and matched with entries in the HMDB database. Metabolic differences between the SLK group and the control group were identified based on multivariate statistical analysis. Open database sources, including SMPDB and MetaboAnalyst, were used to identify metabolic pathways.ResultsAmong 179 metabolites retained for annotation, 133 metabolites were finally identified, among which 50 were found to be significantly changed in SLK patients. Of these 50 metabolites, 31 metabolites significantly increased and 19 metabolites decreased in SLK patients. The altered metabolites are mainly involved in α linolenic acid and linoleic acid metabolism, ketone body metabolism, butyrate metabolism, mitochondrial electron transport chain, carnitine synthesis, and so on. The most significantly changed pathway was linoleic acid metabolism. To explore the utility of tear biomarkers, a model combining 9 metabolites (phenol, ethyl glucuronide, eicosapentaenoic acid, 12-keto-leukotriene B4, linoleic acid, hypoxanthine, triethanolamine, 1-nitrohexane, and terephthalic acid) was selected as a candidate biomarker.ConclusionThe results reveal that SLK has a specific metabolomic profile, of which some key elements can serve as potential biomarkers of SLK for diagnostic and prognostic purposes. The findings of this study are novel and provide a basis for further investigations of the mechanism of SLK.
Highlights
Superior limbic keratoconjunctivitis (SLK) is a bilateral, chronic inflammatory disease that affects the upper bulbar conjunctiva, superior limbus and adjacent cornea [1, 2]
We aimed to identify the metabolites in tears that are pathologically relevant to SLK
All patients were informed about the procedures and provided written informed consent to participate in the study
Summary
Superior limbic keratoconjunctivitis (SLK) is a bilateral, chronic inflammatory disease that affects the upper bulbar conjunctiva, superior limbus and adjacent cornea [1, 2]. There have been some aetiological hypotheses and meaningful explorations, the exact pathogenesis of SLK is unknown. SLK has been characterized by accumulations of mast cells, inflammatory mediators (including stem cell factor, thymic stromal lymphopoietin and matrix metalloproteinases), and tear cytokines (such as monocyte chemoattractant protein-1), which are arousing the interest of researchers [5,6,7]. Targeted treatment based on these hypotheses has poor effects, and the aetiological factors and mechanisms of the disease are still unknown. Molecular alterations of tear fluids would provide a great deal of molecular information that is useful for the diagnosis, prognosis, and treatment of ocular surface diseases [8,9,10,11]. In recent years, exploring disease biomarkers from tears has been of increased interest for many researchers, especially by characterizing the proteomic and metabolomic changes in the tears of different diseases [12,13,14,15,16]
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