Abstract
Purpose: :
To evaluate the efficacy of topical selective phosphodiesterase (PDE) 4 inhibitor in ameliorating dry eye disease (DED).
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: cornea: tears/tear film/dry eye • inflammation • cytokines/chemokines