Expression of Lipid Peroxidation Markers in the Tear Film and Ocular Surface of Patients with Non-Sjogren Syndrome: Potential Biomarkers for Dry Eye Disease

Purpose: To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease.Methods: The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry.Results: The concentrations of HEL, 4-HNE, and MDA were 279.84 69.98 nmol/L, 0.02 +/- 0.01 g/mL, and 3.80 +/- 1.05 pmol/mg in control subjects and 283.21 +/- 89.67 nmol/L (p = 0.97), 0.20 +/- 0.03 g/mL (p < 0.01), and 13.32 +/- 4.03 pmol/mg (p < 0.01) in dry eye patients. 4-HNE and MDA levels significantly correlated with BUT, Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p < 0.05), whereas HEL levels did not correlate with these parameters. Staining intensities for 4-HNE and MDA increased in dry eye patients.Conclusions: The expression of late lipid peroxidation markers, 4-HNE and MDA, increases in the tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease.