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A. Okanobo, S. Chauhan, Y. Chen, Q. Zhang, R. Dana; Therapeutic Efficacy of Topical Phosphodiesterase-4 Inhibitor in Murine Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6276.
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To evaluate the efficacy of topical selective phosphodiesterase (PDE) 4 inhibitor in ameliorating dry eye disease (DED).
Dry eye was induced in female C57BL/6 mice by exposing them to a controlled desiccating environment chamber. Formulations of PDE4 inhibitor (0.05% cilomilast), 0.1% dexamethasone and vehicle were topically applied to different groups of DED mice (n = 8 eyes/group) 3x/daily. DED was scored by corneal fluorescein staining (CFS). Immunohistochemistry and real-time PCR were performed to quantify CD11b+ infiltration and cytokines (IL-1β, IL-1α and TNF-α), mRNA expression, respectively.
DED mice which received cilomilast and dexamethasone showed a significant decrease in the CFS compared to those receiving vehicle alone [mean ± SEM (38% ± 4.8, 35% ± 5.9 vs. 19% ± 5.7, respectively; P < 0.02)], with cilomilast and dexamethasone showing a similar efficacy. Therapy with cilomilast and dexamethasone, compared to the vehicle group, significantly decreased the total number of CD11b+ cells in the cornea (133 ± 7.4 and 130 ± 6.9 vs. 161 ± 7.8, respectively; P < 0.01). The cilomilast and dexamethasone treated eyes also showed a significant decrease in the conjunctival expression of IL-1α and TNF-α (P < 0.03) compared to those receiving vehicle alone. However, only cilomilast showed a significant decrease in the conjunctival expression of IL-1β (P < 0.03). In the cornea, the treatment with cilomilast and dexamethasone showed a significant decrease expression of TNF-α (P < 0.01) compared to vehicle. However, only dexamethasone showed a significant decrease IL-1β in the cornea (P < 0.01). The decrease in the expression levels of IL-1α in the cornea, however, was not statistically significant compared to the vehicle control treated group.
The reversal of clinical signs and underlying inflammatory changes by topical cilomilast treatment clearly suggests that topical PDE-4 blockade could be an effective therapeutic modality for the treatment of DED.
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