Lipidomic analysis of human tear fluid reveals structure-specific lipid alterations in dry eye syndrome

Sin Man Lam,Louis Tong,Bastien Reux,Xinrui Duan,Andrea Petznick,Siew Sian Yong,Cynthia Boo Shiao Khee,Martin J Lear,Markus R Wenk,Guanghou Shui

doi:10.1194/jlr.p041780

Abstract

As current diagnostic markers for dry eye syndrome (DES) are lacking in both sensitivity and specificity, a pressing concern exists to develop activity markers that closely align with the principal axes of disease progression. In this study, a comprehensive lipidomic platform designated for analysis of the human tear lipidome was employed to characterize changes in tear lipid compositions from a cohort of 93 subjects of different clinical subgroups classified based on the presence of dry eye symptoms and signs. Positive correlations were observed between the tear levels of cholesteryl sulfates and glycosphingolipids with physiological secretion of tears, which indicated the possible lacrimal (instead of meibomian) origin of these lipids. Notably, we found wax esters of low molecular masses and those containing saturated fatty acyl moieties were specifically reduced with disease and significantly correlated with various DES clinical parameters such as ocular surface disease index, tear breakup time, and Schirmer's I test (i.e., both symptoms and signs). These structure-specific changes in tear components with DES could potentially serve as unifying indicators of disease symptoms and signs. In addition, the structurally-specific aberrations in tear lipids reported here were found in patients with or without aqueous deficiency, suggesting a common pathology for both DES subtypes.

Highlights

As current diagnostic markers for dry eye syndrome (DES) are lacking in both sensitivity and specificity, a pressing concern exists to develop activity markers that closely align with the principal axes of disease progression
We found the entire class of O-acyl-␻-hydroxy-fatty acids (OAHFAs) to be positively correlated with increasing age (Fig. 1A)
Several phospholipids containing PUFAs were decreased with increasing age, including both diacyl and ether/plasmalogen species (Fig. 1A, supplementary Fig. IC), which might be indicative of increased oxidative stress with advancing age, in corroboration with the previous observation of enhanced oxidation in meibum with aging, based on the ratio of aldehydes to hydroperoxides [15]

Summary

Introduction

As current diagnostic markers for dry eye syndrome (DES) are lacking in both sensitivity and specificity, a pressing concern exists to develop activity markers that closely align with the principal axes of disease progression. We found wax esters of low molecular masses and those containing saturated fatty acyl moieties were reduced with disease and significantly correlated with various DES clinical parameters such as ocular surface disease index, tear breakup time, and Schirmer’s I test (i.e., both symptoms and signs). These structure-specific changes in tear components with DES could potentially serve as unifying indicators of disease symptoms and signs. Tear lipid biomarkers can potentially offer a closer reflection of disease pathophysiology and display better correlation to clinical tests routinely used for dry eye diagnosis, such as the Schirmer’s I test and the tear film breakup time. A comprehensive tear lipidome would facilitate pharmaceutical development of artificial tears for alleviating DES and other ocular diseases

Methods

Results

Discussion

Conclusion