Efficacy of Topical Blockade of Interleukin-1 in Experimental Dry Eye Disease

Abstract

PURPOSE To evaluate the therapeutic efficacy of topical IL-1Ra in the treatment of Dry Eye Disease (DED).

DESIGN Laboratory Investigation.

METHODS DED was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A (CsA), and a vehicle control containing carboxymethylcellulose sodium (CMC) were applied following the induction of dry eye. Corneal fluorescein staining (CFS) was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of IL-1β in the cornea.

RESULTS A significant decrease in CFS was observed following topical treatment with 5% IL-1Ra (P<0.01), 1% methylprednisolone (P<0.01), and 0.05% CsA (P<0.03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P<0.05), corneal lymphatic growth (P<0.05), and corneal IL-1β expression (P<0.003), compared to vehicle treated, were only demonstrated following treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent following CsA treatment.

CONCLUSIONS Topical treatment with IL-1Ra is efficacious in ameliorating the clinical signs of the DED, as well as in reducing underlying inflammation.These effects are comparab le to treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye.