Staurosporine as a potential treatment for Acanthamoeba keratitis using mouse cornea as an ex vivo model

Abstract

Abstract Currently, six different genera were reported to be pathogenic to humans and animals, which the most common being Acanthamoeba genus. Acanthamoeba is a ubiquitous genus of amoebae that can trigger severe and progressive ocular disease kwon as Acanthamoeba Keratitis (AK). Furthermore, actual treatment protocols are based on the combination of different compounds that are not fully effective in eliminating the parasite in ocular infections. Therefore, this leads to an urgent need to develop new compounds to treat Acanthamoeba infections. In the present study, we have evaluated Staurosporine as a potential treatment for Acanthamoeba keratitis using mouse cornea as an ex vivo model, and to investigate its model of action by comparative proteomic analysis. Staurosporine altered the conformation of actin and tubulin cytoskeleton of treated trophozoites of A. castellanii. In addition, proteomic analysis of the effect of Staurosporine on treated trophozoites revelated that this molecule induced an overexpression and a down-regulation of proteins related to functions vital for Acanthamoeba infections. Additionally, obtained results in this study on the ex vivo assay using mouse corneas validate this animal model for the study of the pathogenesis of AK. Finally, Staurosporine eliminated the entire amoebic population and prevented adhesion and infection of amoebae to the epithelium of treated mouse corneas.