Staurosporine as a Potential Treatment for <i>Acanthamoeba</i> Keratitis Using Mouse Cornea as an Ex Vivo Model
2024
Rubén L. Rodríguez-Expósito | Ines Sifaoui | Lizbeth Salazar-Villatoro | Carlos J. Bethencourt-Estrella | José J. Fernández | Ana R. Díaz-Marrero | Robert Sutak | Maritza Omaña-Molina | José E. Piñero | Jacob Lorenzo-Morales
<i>Acanthamoeba</i> is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as <i>Acanthamoeba</i> Keratitis (AK). Furthermore, current treatment protocols are based on the combination of different compounds that are not fully effective. Therefore, an urgent need to find new compounds to treat <i>Acanthamoeba</i> infections is clear. In the present study, we evaluated staurosporine as a potential treatment for <i>Acanthamoeba</i> keratitis using mouse cornea as an ex vivo model, and a comparative proteomic analysis was conducted to elucidate a mechanism of action. The obtained results indicate that staurosporine altered the conformation of actin and tubulin in treated trophozoites of <i>A. castellanii.</i> In addition, proteomic analysis of treated trophozoites revealed that this molecule induced overexpression and a downregulation of proteins related to key functions for <i>Acanthamoeba</i> infection pathways. Additionally, the ex vivo assay used validated this model for the study of the pathogenesis and therapies of AK. Finally, staurosporine eliminated the entire amoebic population and prevented the adhesion and infection of amoebae to the epithelium of treated mouse corneas.
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