Optimization of a histamine-induced allergic conjunctivitis model in Guinea pigs

Allergic conjunctivitis is one of the most common immune diseases in the field of ophthalmology. The number of patients suffering from allergic conjunctivitis has been increasing, and there is still a strong need for development of therapeutic agents for this disease. In drug development, the utmost important point to improve the success probability is to accurately single out good compounds in the early stage of drug development. Therefore, drug efficacy evaluations in the nonclinical stage should be conducted with high reliability and accuracy. However, there are no literatures investigating the preparation and evaluation methods of animal models of conjunctivitis in details nor the standardized criteria. In this study, we verified the reproducibility of an animal model in the previous report and made improvements in test methods focusing on a guinea pig model of histamine-induced allergic conjunctivitis. Furthermore, the drug efficacy evaluation was conducted using a commercially available antihistamine drug, levocabastine hydrochloride, to judge the suitability of the improved model. As a result, the dose level of histamine needed to be increased to use the existing model for drug efficacy evaluation, but allergic-like symptoms were induced very easily and stably in this model. For observations of symptoms of conjunctivitis, we eliminated ambiguity of evaluation by adopting the Draize scale and ensured a higher objectivity on the evaluation method. The drug efficacy evaluation of levocabastine hydrochloride in the prepared model revealed that drug efficacy of the antihistamine drug was captured according to the standardized test method and highly-reproducible results were obtained.