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Susanne Eiglmeier, Zahra Sadrai, Yihe Chen, Sunil K Chauhan, Reza Dana; Effect of the Topical Selective Glucocorticoid Receptor Agonist, Mapracorat, in Experimental Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3219.
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© ARVO (1962-2015); The Authors (2016-present)
This study aimed to evaluate the therapeutic efficacy of mapracorat in a murine model of dry eye disease (DED).
The anti-inflammatory effect of mapracorat was studied in an established murine model of DED. DED was induced by exposure to desiccating stress and subcutaneous injection of scopolamine for the duration of the study. Mapracorat (0.3%, 0.6%, 1%, and 3%), the relevant vehicle, or 1% prednisolone acetate (PA) was topically administered to DED mice twice per day for 7 days. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease progression. At day 11, corneas, conjunctivae, and lymph nodes were harvested to quantitate relevant cytokines via real-time PCR and to characterize the inflammatory infiltrates via flow cytometry analysis.
Compared to the baseline DED (day 3), CFS were significantly decreased in both the 0.6 and 1% mapracorat treated eyes at day 6 (29.4 ± 8.2 %, P = 0.04; 44.5 ± 3.6, % P = 0.003 [mean ± SEM] for the 0.6 and 1% doses respectively), while the other doses of mapracorat, vehicle, and PA 1% were without significant effect. The 0.6% mapracorat-treated eyes also showed a significant decrease in the CFS (44 ± 11.6%, P = 0.006) at day 11. The 0.3%, 1% and 3% concentrations of mapracorat, vehicle and 1% PA had no significant effect on CFS scores at day 11. As compared to the vehicle control, treatment with mapracorat or 1% PA did not significantly reduce corneal or conjunctival expression of IL-1β, IL-23, or IL-17. In the draining lymph nodes only the 3% mapracorat decreased the frequency of IL-17+ cells.
Our data suggest that mapracorat significantly reduced the epitheliopathy associated with dry eye disease. Elucidation of the biochemical mechanisms underlying this effect requires further investigation.
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