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Published on: December 18, 2012
Staurosporine as a Potential Treatment for Acanthamoeba Keratitis Using Mouse Cornea as an Ex Vivo Model
Rubén L Rodríguez-Expósito1,2,3, Ines Sifaoui1,2,3, Lizbeth Salazar-Villatoro4
1Instituto 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.
Abstract:
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.
Insights
Staurosporine effectively treated Acanthamoeba keratitis by disrupting amoebic cytoskeleton and adhesion. This study validates a mouse cornea model for evaluating new Acanthamoeba infection therapies.
Area of Science:
- Ophthalmology
- Microbiology
- Drug Discovery
Background:
- Acanthamoeba Keratitis (AK) is a severe ocular disease caused by Acanthamoeba.
- Current treatments for AK are often ineffective, necessitating novel therapeutic agents.
- A need exists for new compounds to combat Acanthamoeba infections.
Purpose of the Study:
- To evaluate staurosporine as a potential treatment for Acanthamoeba Keratitis (AK).
- To elucidate the mechanism of action of staurosporine against Acanthamoeba.
- To validate a mouse cornea ex vivo model for AK pathogenesis and therapy studies.
Main Methods:
- Ex vivo treatment of mouse corneas with staurosporine.
- Comparative proteomic analysis of Acanthamoeba castellanii trophozoites.
- Assessment of amoebic adhesion and infection following treatment.
Main Results:
- Staurosporine altered actin and tubulin conformation in Acanthamoeba trophozoites.
- Proteomic analysis revealed significant protein expression changes related to infection pathways.
- Staurosporine completely eliminated amoebic populations and prevented epithelial adhesion in treated corneas.
Conclusions:
- Staurosporine demonstrates potent anti-Acanthamoeba activity, including complete elimination and prevention of adhesion.
- The study validates the mouse cornea model for AK research.
- Staurosporine shows promise as a novel therapeutic agent for Acanthamoeba Keratitis.
