Amelioration of Murine Dry Eye Disease by Topical Antagonist to Chemokine Receptor 2

Abstract

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 1α and 1β in the cornea, and tumor necrosis factor α and interleukin 1β 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.