Therapeutic efficacy of topical blockade of substance P in experimental allergic red eye.

PURPOSE: Allergic conjunctivitis is the most common cause leading to ocular redness (OR). Herein, using an animal model of allergic OR, we evaluated the therapeutic efficacy of topical blockade of substance P (SP) in treating red eye. METHODS: Allergic OR was induced in guinea pigs with topical histamine. Ocular SP was blocked using a specific SP receptor (neurokinin-1 receptor, NK1R) antagonist, L-703,606, via topical application 10 min before or 10 min after histamine instillation. Animal eyes were examined and a series of images were taken for up to 60 min post-OR induction. The severity of redness was analyzed using the quantitative ocular redness index (ORI). At the end of clinical examination, conjunctival tissues were collected for histological examination of conjunctival blood vessels and infiltrating eosinophils and neutrophils. In addition, SP concentration was quantified in the tear fluid and expression levels of inflammatory cytokines were assessed in the conjunctival tissues. RESULTS: Topical histamine application successfully induced red eye, evidenced by the significantly increased ORI during the observation period, with peak values at 10 min, along with significantly increased levels of SP in the tears. Topical treatment with L-703,606, either before histamine application or at the time of peak ORI, effectively reduced ORI and suppressed conjunctival blood vessel dilation, along with decreased eosinophil and neutrophil infiltration, and inflammatory cytokine expression in the conjunctiva, as well as reduced SP levels in the tears. CONCLUSIONS: Topical blockade of SP effectively prevents and treats allergy-related ocular redness by suppressing blood vessel dilation and allergic inflammation.