Clinical and histological evaluation of sirolimus eye drops and sirolimus intraperitoneal injection in mice with experimental allergic conjunctivitis

摘要

Purpose : Allergic conjunctivitis often requires immunomodulatory agents for effective management. The purpose of this study is to examine the therapeutic effect of topical and systemic administration of sirolimus in a mouse model of allergic conjunctivitis. Methods : BALB/C mice, age 6a??8weeks, weighed 20a??25g, were sensitized by footpad injection of 50 mg of SRW pollen absorbed on Imject Alum (5 mg) on day 0 and were challenged by topical instillation of 5?μL of 5mg SRW pollen once a day from days 10 to 16. Mice were randomly assigned topical treatment groups: Normal control (non-sensitizationon-challenge, Ctl), Model (sensitization/challenge, Mod), Blank control (Model + vehicle, Blk), 0.1% sirolimus eye drop (Srl), 0.1% olopatadine (Opd). For systemic study, animals were divided into groups: Normal control (non-sensitizationon-challenge, Ctl), Model (sensitization/challenge, Mod), Blank control (Model+vehicle, Blk),1mg/kg/day sirolimus intraperitoneal injection (SrlS1), 2mg/kg/day sirolimus intraperitoneal injection (SrlS2). All mice underwent clinical evaluation, including clinical sore, palpebral fissure height and scratching frequency, the conjunctiva were removed for histological analysis on day 17. Results : For sirolimus eye drops, the palpebral fissure heights of Srl and Blk were 2.06mm and 2.22mm, and the scratching frequencies were 29.2/15min and 28.6/15min, the number of eosinophils were 25.3/visual field and 25.6/visual field. For sirolimus intraperitoneal injection, the average size of palpebral fissure heights were 2.01mm, 2.04mm and 2.00mm for the SrlS1, SrlS2 and Blk respectively, and the scratching frequencies were 28.14/15min, 27.96/15min and 30.27/15min, the number of eosinophils were 23.93/visual field, 24.60/visual field and 24.85/visual field. Neither the topical nor the systemic administration of sirolimus was found significant difference in the clinical evaluation (clinical scores, palpebral fissure heights and scratching frequencies) and histological analysis (eosinophil and mast cells counting) among the treatment groups as compared to controls (P???0.05). Significant improvements were found in both the in vivo and in vitro observation in animals that applied 0.1% olopatadine eye drop (P???0.05). Conclusions : The administration of sirolimus may not be beneficial in the treatment of experimental allergic conjunctivitis in mice. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.