Expression of CCR5 and Its Ligands CCL3,-4, and-5 in the Tear Film and Ocular Surface of Patients with Dry Eye Disease

Purpose: To evaluate the expression of CCR5 and its ligands CCL3, CCL4, and CCL5 in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. Materials and Methods: The concentrations of CCL3, CCL4, and CCL5 were measured using enzyme-linked immunosorbent assay in tear samples obtained from forty-three patients with dry eye (17 SS and 26 non-SS patients) and 20 control subjects. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. Expression of the chemokines and their receptor in the conjunctiva was evaluated using immunohistochemistry. Flow cytometry was performed to detect CCR4+CD4+, CCR5+CD4+, and CCR6+CD4+ cells in the conjunctiva. Results: The concentrations of CCL3, CCL4, and CCL5 were 25.3 +/- 24.2, 4.65 +/- 3.21, and 93.12 +/- 26.31 pg/mL in control subjects, 92.33 +/- 13.23, 263.13 +/- 116.13, and 253.64 +/- 46.29 pg/mL in patients with non-SS, and 215.56 +/- 36.1, 697.85 +/- 185.65, and 456.12 +/- 92.82 pg/mL in patients with SS. The concentrations showed a significant increase in tears of SS patients compared with those of non-SS patients and control subjects (p < 0.05). CCL5 levels showed significant correlation with tear film break-up time, basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (p < 0.01). Staining for the chemokines and their receptor increased in dry eye patients, especially in those with SS patients. Flow cytometry demonstrated increased numbers of CCR5+CD4+, and CCR6+CD4+ cells in dry eye patients in contrast to CCR4+CD4+ cells. Conclusions: Expression of CCR5 and its ligands CCL3, CCL4, and CCL5 increase in the tear film and ocular surface of patients with dry eye syndrome, especially in those with SS. CCL5 levels correlate significantly with various tear film and ocular surface parameters.