Abstract
Purpose :
To test the safety and efficacy of two Aprepitant formulations (A and B) in a mouse model of Benzalkonium Chloride (BAK)-induced dry eye disease.
Methods :
The safety and efficacy of Aprepitant were analyzed in 60 male C57BL/6N mice. In vivo corneal fluorescein staining was used to assess corneal epithelial disease. Dry eye disease was induced by topical application of 0.2% BAK twice a day for 1 week, followed by once a day application for 1 week. After the first week, mice were randomized into five topical treatment groups: Aprepitant A (n=10) and B (n=10) formulations, 2mg/ml dexamethasone (n=10), Aprepitant vehicle (n=10), 0.2% hyaluronic acid (n=10), or no treatment (n=10). Biomicroscopy images were taken on days 0, 3, 5, 7, 9, 12, and 14 with a slit-lamp. Corneal sensitivity, phenol red and eye wiping tests were performed to assess nerve function, tear secretion and ocular pain. Leukocyte infiltration and corneal nerve density were quantified on whole-mounted corneas after seven days of treatment. One-way ANOVA and Tukey’s multiple comparison tests were used to compare different treatment groups. A p-value lower than 0.05 was considered statistically significant.
Results :
Topical administration of Aprepitant formulation A ameliorated corneal epithelial disease in the DED model. Mice treated with Aprepitant formulation A showed lower ocular pain than mice treated with vehicle (p=0.007) and dexamethasone (p=0.021). In addition, mice treated with both A and B Aprepitant formulations had preserved corneal sensitivity when compared with Aprepitant vehicle and dexamethasone-treated mice (p<0.001). Moreover, Aprepitant A-treated mice showed reduced corneal infiltration of leukocytes (p<0.05) and improved corneal nerve density versus dexamethasone (p<0.001). No statistically significant increase in tear fluid secretion was observed with any of the treatments.
Conclusions :
Aprepitant formulation A restored epithelial integrity, corneal sensitivity and improved nerve density. Besides, it reduced leukocyte infiltration and ocular pain in a pre-clinical mouse model of DED. Our data suggest that Aprepitant A formulation could be a safe and effective option in the treatment of DED.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.