Integrated Tear Proteome and Metabolome Reveal Panels of Inflammatory-Related Molecules via Key Regulatory Pathways in Dry Eye Syndrome

Abstract

Dry eye syndrome (DES) is a growing public health concern with a high global prevalence; however, the fundamental processes involved in its pathogenic mechanisms remain poorly understood. In the present study, we applied nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies on tear samples obtained from 18 dry eye patients and 19 healthy controls for integrated proteomic and metabolomic analyses. Overall, 1031 tear proteins were detected, while 190 proteins were determined to be significantly expressed in dry eye patients. Further functional analysis suggested that various biological processes were highly expressed and involved in the pathogenesis of DES, especially immune and inflammatory processes. In total, 156 named metabolites were identified, among which 34 were found to be significantly changed in dry eye patients. The results highlighted the key elements, especially inflammatory-related proteins and metabolites that played important roles in the development of DES. Further, the regulatory roles of primary pathways, including complement and coagulation cascades, glycolysis/gluconeogenesis, and amino acid metabolism, were also identified as processes involved in DES. Collectively, our work not only provided insight into the potential biomarkers of DES for diagnostic and prognostic purposes but extended our knowledge of the physiopathology of this syndrome.

Tear Metabolomics in Dry Eye Disease: A Review

“…The interview, questionnaire, and/or ophthalmologic examinations have previously been used individually, or in combination, to screen and group DED patients for metabolomics studies of tears. Using this approach, distinct metabolomic fingerprints of DED patient and control groups were found [101,102,103,104,105,106,107] and additional severity-associated subgroups, mild-to-moderate and moderate, were identified in the DED patients [103]. Thus, there is considerable potential for metabolomics in the classification of DED.…”

“…Their correlations with clinical tests of DED have been documented [153]. Finally, Chen et al [107] evaluated the metabolomic profile of tears from DED and healthy groups using nanoLC–MS. They identified a total of 156 metabolites, of which 32 were significantly changed ( p < 0.05) in patients with DED.…”

Metabolomic analysis in ophthalmology

“…These results indicated that inflammatory related metabolites and pri-mary pathways like glycolysis and gluconeogenesis, amino acid metabolism may play regulatory role in DES (ref. 44 ).…”

The expression of miRNA-146a-5p and its mechanism of treating dry eye syndrome

“…Dry eye syndrome, also known as keratoconjunctivitis, is a tear and ocular surface disease caused by a variety of factors, the main causes were decreased tear lm stability and ocular surface damage induced by tear uid and quantitative or kinetic abnormalities [1]. The disease is accompanied with eye dryness, redness, foreign body sensation and other ocular surface discomfort and visual impairment [2].…”