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.


CONCLUSIONS
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.
Goyal
Sunali
S
Schepens Eye Research Institute, Boston, MA 02114, USA.
Chauhan
Sunil K
SK
Zhang
Qiang
Q
Dana
Reza
R
D000287:Administration, Topical; D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D003228:Conjunctiva / Q000276:immunology; D003315:Cornea / Q000276:immunology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D039481:CD11b Antigen; D017252:CD3 Complex; C515335:Ccr2 protein, mouse; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger; D054390:Receptors, CCR2; D014409:Tumor Necrosis Factor-alpha