Expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome

Abstract

Purpose: To investigate the expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome.

Methods: Thirty-three patients with dry eye (16 with and 17 without Sjögren's syndrome) and 15 control subjects were recruited. The concentrations of CXCL9, -10, and -11 in tears were measured with enzyme-linked immunosorbent assays. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. The expression of CXCL9, -10, -11, and CXCR3 in the conjunctiva was evaluated by using immunohistochemistry. Flow cytometry was performed to count CXCR3(+) cells and CXCR3(+)CD4(+) cells in the conjunctiva.

Results: The concentrations of CXCL9, -10, and -11 were 1,148 +/- 1,088, 24,338 +/- 8,706, and 853 +/- 334 pg/mL, in the patients with dry eye, and 272 +/- 269 (P = 0.01), 18,149 +/- 5,266 (P = 0.02), and 486 +/- 175 (P < 0.01) pg/mL in the control subjects, respectively. The concentrations significantly increased in tears of the patients with Sjögren's syndrome compared with those of the patients with non-Sjögren's dry eye (P < 0.05). CXCL10 levels correlated significantly with basal tear secretion, and CXCL11 levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (P < 0.05). Staining for CXCL9, -10, -11, and CXCR3 increased in patients with dry eye, especially in the patients with Sjögren's syndrome. Flow cytometry demonstrated an increased number of CXCR3(+) and CXCR3(+)CD4(+) cells in all the patients with dry eye.

Conclusions: Expression of CXCL9, -10, -11, and CXCR3 increased in the tear film and ocular surface of patients with dry eye syndrome, especially in those with Sjögren's syndrome. CXCL11 levels correlated significantly with various tear film and ocular surface parameters. (ClinicalTrials.gov number, NCT00991679.).

Figures

Figure 1.

CXCL9 (A), -10 (B), and -11 (C) levels in tears of control subjects, patients with non-Sjögren's dry eye (non-SS), and those with Sjögren's syndrome (SS).

Figure 2.

Correlation between tear CXCL11 level and tear surface parameters including corneal sensitivity (A), tear film BUT (B), basal tear secretion (C), tear clearance rate (D), keratoepitheliopathy score (E), and conjunctival goblet cell density (F).

Figure 3.

Immunohistochemistry for CXCL9, -10, and -11, and CXCR3 in the conjunctiva of the control subjects, the patients with non-Sjögren's dry eye (non-SS), and the patients with Sjögren's syndrome (SS).

Figure 4.

Mean immunostaining intensity for CXCL9 (A), -10 (B), and -11 (C) and mean density of CXCR3+ cells (D) in the conjunctiva.

Figure 5.

Two-color flow cytometry showing CXCR3+ and CD4+ cells in the conjunctiva of the control subjects (A), the patients with non-Sjögren's dry eye (B), and the patients with Sjögren's syndrome (C).