Amelioration of murine dry eye disease by topical antagonist to chemokine receptor 2.

OBJECTIVE To determine the effect of a topical antagonist to the chemokine receptor 2 (CCR2) in a murine model of dry eye disease. METHODS The effects of a topical CCR2 antagonist and a vehicle control treatment were studied in murine dry eyes. A controlled environment chamber induced dry eye by exposing mice to high-flow desiccated air. Corneal fluorescein staining and enumeration of corneal CD11b(+) and conjunctival CD3(+) T cells were performed in the different groups. Real-time polymerase chain reaction was performed to quantify expression of different inflammatory cytokine transcripts in the cornea and conjunctiva. RESULTS Eyes receiving the formulation containing CCR2 antagonist showed a significant decrease in corneal fluorescein staining and decreased infiltration of corneal CD11b(+) cells and conjunctival T cells compared with the vehicle-treated and untreated dry eye groups. The CCR2 antagonist also significantly decreased messenger RNA expression levels of interleukins 1alpha and 1beta in the cornea, and tumor necrosis factor alpha and interleukin 1beta in the conjunctiva. CONCLUSION Topical application of CCR2 antagonist is associated with significant improvement in dry eye disease and is reflected by a decrease in inflammation at the clinical, molecular, and cellular levels. Clinical Relevance Topical application of CCR2 antagonist may hold promise as a therapeutic modality in dry eye disease.