Staurosporine as a Potential Treatment for <i>Acanthamoeba</i> Keratitis Using Mouse Cornea as an Ex Vivo Model
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
Affiliations
Rubén L. Rodríguez-Expósito
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Tenerife, Spain
Ines Sifaoui
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Tenerife, Spain
Lizbeth Salazar-Villatoro
Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico 07360, Mexico
Carlos J. Bethencourt-Estrella
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Tenerife, Spain
José J. Fernández
Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), 38203 San Cristóbal de La Laguna, Tenerife, Spain
Ana R. Díaz-Marrero
Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), 38203 San Cristóbal de La Laguna, Tenerife, Spain
Robert Sutak
Department of Parasitology, Faculty of Science, Charles University, BIOCEV, 252 50 Vestec, Prague, Czech Republic
Maritza Omaña-Molina
Facultad de Estudios Superiores Iztacala, Medicina, National Autonomous University of Mexico (UNAM), Tlalnepantla 54090, Mexico
José E. Piñero
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Tenerife, Spain
Jacob Lorenzo-Morales
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Tenerife, Spain
Acanthamoeba is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as Acanthamoeba 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 Acanthamoeba infections is clear. In the present study, we evaluated staurosporine as a potential treatment for Acanthamoeba 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 A. castellanii. In addition, proteomic analysis of treated trophozoites revealed that this molecule induced overexpression and a downregulation of proteins related to key functions for Acanthamoeba 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.