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Amelioration of Murine Dry Eye Disease by Topical Antagonist to Chemokine Receptor 2
Sunali Goyal, MD;
Sunil K. Chauhan, PhD;
Qiang Zhang, MD;
Reza Dana, MD, MSc, MPH
Arch Ophthalmol. 2009;127(7):882-887.
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 1 and 1β in the cornea, and tumor necrosis factor 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.
Author Affiliations: Schepens Eye Research Institute (Drs Goyal, Chauhan, Zhang, and Dana), Department of Ophthalmology, Harvard Medical School (Drs Goyal, Chauhan, Zhang, and Dana), and Massachusetts Eye and Ear Infirmary (Dr Dana), Boston, Massachusetts.
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