Staurosporine as a Potential Treatment for Acanthamoeba Keratitis Using Mouse Cornea as an Ex Vivo Model

IF 4.9 2区医学 Q1 CHEMISTRY, MEDICINAL

Marine Drugs Pub Date : 2024-09-18 DOI:10.3390/md22090423

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

{"title":"Staurosporine as a Potential Treatment for Acanthamoeba Keratitis Using Mouse Cornea as an Ex Vivo Model","authors":"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","doi":"10.3390/md22090423","DOIUrl":null,"url":null,"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.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"7 1","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Marine Drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/md22090423","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

以小鼠角膜为体内外模型，用司陶罗孢林治疗棘阿米巴角膜炎的潜力

阿卡阿米巴是一种无处不在的阿米巴虫属，可引发严重的渐进性眼部疾病，即阿卡阿米巴角膜炎（AK）。此外，目前的治疗方案基于不同化合物的组合，但并不完全有效。因此，寻找治疗棘阿米巴感染的新化合物的迫切性显而易见。在本研究中，我们以小鼠角膜为体外模型，评估了施陶罗索林治疗阿卡阿米巴角膜炎的潜力，并进行了比较蛋白质组分析，以阐明其作用机制。研究结果表明，司陶孢林改变了卡氏阿卡胞虫滋养体中肌动蛋白和微管蛋白的构象。此外，对处理过的滋养体进行的蛋白质组学分析表明，该分子诱导了与棘阿米巴感染途径关键功能相关的蛋白质的过表达和下调。此外，所使用的体内外试验也验证了该模型在研究 AK 发病机制和疗法方面的有效性。最后，石杉碱消除了整个阿米巴虫群，并防止了阿米巴虫粘附和感染处理过的小鼠角膜上皮。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Marine Drugs 医学-医药化学

CiteScore

9.60

自引率

14.80%

发文量

671

审稿时长

1 months

期刊介绍： Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.