Abstract
Purpose :
Allergic conjunctivitis is an inflammatory eye disease mediated by conjunctival eosinophilic infiltration and Th2 type immune responses. This present study aims to elucidate the role of rapamycin, an mTOR inhibitor, on OVA-induced experimental allergic conjunctivitis (EAC).
Methods :
BALB/c mice were challenged with ovalbumin via the conjunctival sac after systemic challenge with OVA in aluminum hydroxide. Control PBS group and non-treated OVA groups were injected with vehicle intraperitoneally and the rapamycin-treated group were injected with 2mg/kg of rapamycin 30 min before OVA challenge. For topical application of rapamycin, an eye drop concentration of 0.04% was administered 30 mins before OVA challenge in the conjunctival sac.
Results :
Rapamycin administration intraperitoneally markedly reduced clinical signs, OVA-specific IgE and IgG1/G2a ratio in serum, and conjunctival eosinophilic infiltration. Infiltrations of CD11c+ dendritic cells and CD4+ T cells, and the expressions of chemokines and adhesion molecules in the conjunctiva were decreased in rapamycin-treated mice, as well as decreased Th2 cytokines in the cervical lymph nodes compared to non-treated OVA mice. The expression of mTOR signaling proteins was increased in EAC and reduced by rapamycin treatment. Topical application of rapamycin was also proved to show reduced clinical signs, eosinophil infiltration, and Th2 type immune responses comparable to those from intraperitoneal injection of rapamycin.
Conclusions :
These findings elucidate the attenuating effects of rapamycin in an OVA-induced EAC model and impart various therapeutic implications of rapamycin for the treatment of allergic conjunctivitis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.