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Giulio Ferrari, Fabio Bignami, Paolo Rama; Topical Neurokinin 1 receptor antagonist as a treatment of ocular surface inflammation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):978.
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© ARVO (1962-2015); The Authors (2016-present)
To test safety and efficacy of topical application of the Neurokinin 1 receptor antagonist Fosaprepitant for the treatment of corneal inflammation in an alkali burn model.
Thirty female, 6- to 8-week-old, C57/BL6 mice were induced corneal inflammation by means of alkali burn. Seven days later, topical treatment with Fosaprepitant 10mg/ml, 6 times a day in the right eye was started and continued for 10 days. A second group of thirty causticated mice was treated with saline, as a control. Finally, 10 healthy mice were applied 10mg/ml topical Fosaprepitant for 10 days to test for potential toxicity to the epithelium and/or corneal nerves. Inflammatory cell infiltration was quantified by means of: (a) immunofluorescence microscopy of CD45+ cells in the stroma of corneal whole mounts, and (b) flow cytometry of dissociated corneal stromal cells, stained with: CD45, CD11b, F4/80, Ly6G/Ly6C(GR1). Toxicity was evaluated by quantification of corneal epithelial defects (diamidino-phenyil-indole fluorescence microscopy) and corneal nerve density (beta-3 tubulin immunofluorescence) on corneal whole mounts. Differences between groups were assessed using unpaired t-test or Mann-Whitney U test, as appropriate.
Treatment with topical Fosaprepitant was effective in reducing inflammatory cell infiltration. Specifically: (i) CD45+ leukocyte infiltration quantified in corneal whole mounts was reduced by 33% (P < 0.05). Moreover, flow cytometry analysis showed a 54% reduction (P < 0.05) of myeloid infiltrating cells (CD45+7AAD-CD11b+) in the cornea after Fosaprepitant treatment. Specifically, Fosaprepitant treatment induced: (i) 75% decrease of GR1dim F4/80+ macrophages (P< 0.01), and (ii) 72% decrease of GR1high F4/80- neutrophils (P< 0.05). Interestingly, Neurokinin 1 receptor was expressed by 69±16% of stromal CD45+ cells.When Fosaprepitant was administered on normal corneas to test for toxicity, no epithelial defects were detected; corneal nerves exhibited normal morphology and their density was not significantly different in the treated group (P=0.76).
We conclude that topical application of Fosaprepitant can significantly inhibit inflammatory cell infiltration in the cornea after inflammation has occurred. In addition, topical application of Fosaprepitant did not appear toxic for the corneal epithelium or corneal nerves.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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