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James McLaughlin, Andy Whitlock, Laura Belen, Jennifer Brackett, Burkhard Blank; Evaluation of the Effects of Cis-UCA in a Murine Model for Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2554.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to investigate the potential of topically applied Cis-urocanic acid (Cis-UCA) in reducing the signs of allergic conjunctivitis.
We used a murine model of allergic conjunctivitis based upon the allergen challenge paradigm. Animals were sensitized with subcutaneously injected short ragweed (SRW) allergen, and then challenged 18 days later with topical SRW. Following challenge mice were randomized into treatment groups (n=10) and given test compounds QID for 4 days. Challenges were repeated BID on the third and fourth days of treatment; their responses to allergen were evaluated after challenges 1 and 4. Cis-UCA was provided at concentrations of 0.0, 1.0, and 2.5%. Additional test agents included olopatadine 0.1% (Patanol®) and prednisolone (Pred) acetate 1.0% as positive controls. Cis-UCA vehicle was used as the negative control. Following challenges hyperemia, squinting, discharge or tearing, and lid swelling were evaluated using a novel Micron III imaging system. Allergic responses were graded on a 0-4 scale using the proprietary Ora clinical grading scale.
For the first challenge, only the Pred reduced hyperemia significantly; animals receiving either Pred or olopatadine showed significant reduction for challenge 4. None of the scores for squinting showed a significant difference, although the Pred and the 2.5% Cis-UCA were the lowest average scores. A combined score averaged from hyperemia and squinting scores showed a clear tendency toward reduced scores for olopatadine, Pred, and Cis-UCA 2.5%, with the Pred and the Cis-UCA scores significantly different from vehicle at p values of 0.05 and 0.001 respectively.
Mouse models provide a useful means to screen potential drugs for clinical trials. In this study we compared the efficacy of Cis-UCA, to several drugs currently used to treat ocular allergic conjunctivitis. Olopatadine is a drug of choice for seasonal allergies, while Pred is used to treat more severe or chronic allergies. In this trial, Cis-UCA 2.5% behaved similar to the steroid comparator. Our results provide encouraging data that suggest that this new class of anti-inflammatories may be useful therapeutic for acute and chronic allergic conjunctivitis.
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