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Zahra Sadrai, William Stevenson, Andre Okanobo, Yihe Chen, Jing Hua, Sunil Chauhan, Reza Dana; Topical Blockade of Phosphodiesterase 4 (PDE4) Ameliorates Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2341.
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To evaluate the therapeutic efficacy of a topical phosphodiesterase 4 (PDE4) inhibitor on dry eye disease (DED).
The therapeutic efficacy of PDE4 inhibitor was studied in an established murine model of dry eye. Formulations of 0.05% PDE4 inhibitor (cilomilast), the relevant vehicle, or cyclosporine was administered to different groups of DED mice (n=8 eyes/group) 3 times daily. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease progression. Real-time PCR and flow cytometry analysis were performed to evaluate inflammatory cytokine expression and cell infiltration in the ocular surface and draining lymph nodes.
Compared to the relevant vehicle, cilomilast-treated eyes showed a significant decrease in the CFS [mean ± SEM (40% ± 6.1 P = 0.05)]. There was no significant difference between cyclosporine- and cilomilast-treated eyes in respect to CFS reduction. Compared to the vehicle control, treatment with cilomilast reduced conjunctival expression of IL-17 and IL-23 (P <0.05) and Th17 infiltration. Topical cyclosporine did not significantly reduce the conjunctival expression of either IL-17 or IL-23 compared to the cilomilast-treated group. Compared to the vehicle control, cilomilast showed significant decrease in the expression of IL-17 and IL-23 (P <0.05) in the draining lymph nodes.
Our data suggest that topical treatment with cilomilast significantly reduces the clinical severity and progression of the disease which is parallel by a reduction in the expression of Th17-associated cytokines at the ocular surface and draining lymph nodes.
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