Association between dry eye and inflammatory response mediated by CCR5 and CXCR3 and their ligands

Sustained abnormal tear secretion in dry eye patients may lead to ocular surface and lacrimal glands in the state of long-term inflammatory cell infiltration. Lacrimal gland suffers immune attack by lymphoproliferative, and inflammation interferes normal gland secretion, in which chemokines and their receptors on lymphocytes play a key role.

This study was to investigate the inflammation mechanism of delayed allergy induced by Th1 cell in the development of dry eye.

Sixty eyes of 30 patients with dry eye and matched 30 healthy volunteers were enrolled in Affiliated First Hospital of Xinjiang Medical University from June to December in 2012. SchirmerⅠtest (SⅠt), break up time (BUT) of tear and corneal fluorescence stain (FLS) were performed on the subjects, and conjunctiva epithelial cells were obtained using cytological method of conjunctiva imprinting. Positive cell rates of CC chemokine receptor 5 (CCR5) and CXC chemokine receptor 3 (CXCR3) were detected by flow cytology, and the relative expression levels of regulated upon activation of normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α and MIP-1β, monokine induced by interferon-γ (IFN-γ) (MIG), interferon-γ inducible protein 10 (IP10) and interferon-inducible T-cell α chemoattractant (I-TAC) mRNA were quantitatively assayed by real-time PCR. Differences of the positive rates of CCR5, CXCR3 and lignds were compared between dry eye group and normal control group. Relationship between the positive rates of CCR5, CXCR3 and BUT, SⅠt, FLS scores was analyzed.

The values of BUT, SⅠt were (2.90±1.37) seconds and (4.00±2.49) mm/5 minutes in the dry eye group, which were significantly lower than (8.56±4.69) seconds and (11.31±5.23) mm/5 minutes in the normal control group (t=3.172, 2.186, both at P<0.05). FLS scores, positive rates of CCR5 and CXCR3 were 0.90±0.57, (3.38±0.66) % and (2.64±0.47)% in the dry eye group, showing significant elevations in comparison with 0.14±0.06, (2.12±0.21) % and (1.12±0.11) % in the normal control group (t=2.297, 3.151, 5.454, all at P<0.05). In the dry eye group, the masculine rate of CCR5 was negatively correlated with BUT and SⅠt (r=-0.473, -0.385, both at P<0.05). The masculine rate of CXCR3 was negatively correlated with BUT and SⅠt (r=-0.753, -0.684, both at P<0.05). No considerable correlations between the positive rate of CCR5 with the positive rate of CXCR3 or FLS scores (r=0.231, 0.336, both at P<0.05). The relative expression levels of RANTES, MIP-1α, MIG and IP10 mRNA in the dry eye group were significantly higher than those in the normal control group (t=3.091, 2.894, 2.688, 2.245, all at P<0.05), but there were no significant differences in the relative expression levels of MIP-1β and I-TAC mRNA between the two groups (t=0.512, 1.979, both at P>0.05). The positive correlations were seen between the masculine rate of CCR5 with the relative expression of RANTES or MIP-1α mRNA (r=0.473, 0.285, both at P<0.05), but there was no obvious correlation between the masculine rate of CCR5 and the MIP-1β mRNA expression(r=0.214, P>0.05). In addition, the masculine rate of CXCR3 was positive correlated with the expressions of MIG and IP10 mRNA (r=0.553, 0.314, both at P<0.05), whereas the masculine rate of CXCR3 was not related to the expression of I-TAC mRNA (r=0.364, P>0.05).

Dry eye is probably along with the long-term infiltration of inflammatory cells. The delayed allergy induced by Th1 cells and the nature killed cells is probably the primary cause to xerophthalmia. CCR5, CXCR3 and their ligands might be the regulative targets in the inflammation mechanism of dry eye.