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Fabio Bignami, Anna Lorusso, Paolo Rama, Giulio Ferrari; Topical Fosaprepitant Treatment in Established Corneal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3518.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal avascularity is important for a clear vision. Preexisting corneal stromal vessels are a strong risk factor for immune rejection after corneal transplantation. Available medical therapies for established corneal neovascularization (CNV) are poorly effective and associated with significant side effects.The activation of neurokinin-1 receptor (NK-1R) through its ligand Substance P promotes ocular inflammation and CNV.We tested the safety and efficacy of topical NK-1R antagonist Fosaprepitant in the treatment of animal model with established CNV.
Twenty alkali burned C57BL/6 mice received Fosaprepitant 10 mg/mL, topically 6 times a day in the right eye for 10 days. A second group was treated with normal saline, as control. The treatment was started 7 days after corneal injury, when CNV was established. Ten healthy mice received the same topical treatment for 10 days to evaluate Fosaprepitant safety. Hemangiogenesis and lymphangiogenesis were automatically measured by means of VesselJ plugin (ImageJ). Leukocyte infiltration and secondary outcome measures, such as opacity and corneal fluorescein, were evaluated.Differences between groups were assessed using unpaired t-test or Mann-Whitney U test, as appropriate.
Topical Fosaprepitant administration induced a significant reduction of (i) CD31+ blood corneal neovessels (-27%, P = 0.0132), (ii) LYVE1+ lymphatic corneal neovessels (-31%, P = 0.0118), and (iii) CD45+ leukocyte infiltration (-36%; P = 0.0237). Moreover, Fosaprepitant-treated corneas showed a reduction in opacity and corneal fluorescein staining, suggesting reduced inflammation. Finally, topical Fosaprepitant resulted safe on ocular surface: no signs of hyperemia/conjunctivitis, opacity, perforations or epithelial defects were detected.
All these data suggest that NK-1R antagonist, such as Fosaprepitant, could be a new promising therapeutic tool to induce regression of established CNV.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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