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Giulio Ferrari, Fabio Bignami, Chiara Giacomini, Paolo Rama; SUBSTANCE P EXPRESSION AND ITS INHIBITION IN CORNEAL NEOVASCULARIZATION. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3243.
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© ARVO (1962-2015); The Authors (2016-present)
To quantify expression of Substance P in corneal neovascularization (CNV) and to test whether local administration of a Substance P receptor antagonist (NK1R-a) is toxic to the ocular surface and may reduce vessel growth in two different animal models of CNV.
Five-week old C57/BL6 male mice were used. To quantify Substance P, eight mice received a corneal caustication with 1N NaOH in their right eye and the cornea of six mice was sutured intrastromally. Nine days later, the cornea was removed, homogenized and prepared for the Substance P EIA assay. To test whether inhibition of Substance P may reduce CNV, twelve causticated mice received NK1R-a dissolved in saline six times a day topically for four days. Ten sutured animals received subconjunctival NK1R-a dissolved in saline every 48 hours for 10 days. Finally, 16 animals served as controls and received saline (6 topically; 6 subconjunctivally). Following treatment, animals were sacrificed, corneas removed and stained for CD31 and LYVE-1. Images of corneal whole-mounts were obtained with a confocal microscopy and mounted. Neovascular area was measured as a ratio between the area of the cornea covered by neovessels and the total area of the cornea using ImageJ software. Finally, four normal mice were used to test toxicity of topical NK1R-a.
Substance P corneal concentration was 6,336 pg/ml in control corneas and increased to 8,702 pg/ml (P<0.05) in causticated corneas and 12,320 pg/ml in sutured corneas (P<0.001). Following topical administration of an NK1-R antagonist in the caustication model, both lymphatic and blood neovascular area were significantly reduced (P<0.01). Subconjunctival administration of NK1R-a was effective in reducing lymphangiogenesis in the suture model (P<0.01). Topical administration of NK1R-a was not toxic when administered to normal eyes up to 9 days.
Corneal neovascularization is a highly prevalent disorder as it is estimated that it may be present in up to 10% of blinding diseases worldwide. Therapeutic options are limited and associated with significant side effects. Substance P antagonists appear to be effective and non toxic in the local treatment of corneal neovascularization in two different animal models.
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