Lee Min Hee, Wiedman Gregory, Park Steven, Mustaev Arkady, Zhao Yanan, Perlin David S
Public Health Research Institute, New Jersey Medical School, Rutgers, Newark, NJ, USA.
Med Mycol. 2018 Oct 1;56(7):796-802. doi: 10.1093/mmy/myx125.
Fungal keratitis is a leading cause of ocular morbidity and blindness in developing countries. Diagnosing fungal keratitis currently relies on a comparative evaluation of corneal biopsy or scraping using a direct microscopy and culture results. These methods not only carry the risk of developing complications due to the invasive tissue sampling but also are largely limited by diagnostic speed and accuracy, making it difficult to initiate timely appropriate antifungal therapy. Therefore, rapid and noninvasive diagnostic tools are a pressing need for improved outcomes for fungal keratitis. Taking advantage of the highly specific fungal cell targeting properties of caspofungin, we have developed a fluorescent chemical probe with high selectivity against fungal pathogens. Utilizing fluorescence imaging technology, we have demonstrated a highly specific and sensitive detection of Aspergillus in a fungal keratitis model in mice as early as 5 min post-topical application of the probe. Our results indicate that a fluorescence-mediated platform can be used as a rapid (<10 min) alternative to conventional methods for detecting Aspergillus, and potentially other fungi, in fungal infections of the cornea.
真菌性角膜炎是发展中国家眼部发病和失明的主要原因。目前,真菌性角膜炎的诊断依赖于对角膜活检或刮片进行直接显微镜检查和培养结果的比较评估。这些方法不仅因侵入性组织采样而有发生并发症的风险,而且在很大程度上受到诊断速度和准确性的限制,难以及时启动适当的抗真菌治疗。因此,快速且非侵入性的诊断工具对于改善真菌性角膜炎的治疗效果至关重要。利用卡泊芬净对真菌细胞具有高度特异性的靶向特性,我们开发了一种对真菌病原体具有高选择性的荧光化学探针。利用荧光成像技术,我们证明了在小鼠真菌性角膜炎模型中,早在局部应用探针后5分钟就能高度特异性和灵敏地检测到曲霉菌。我们的结果表明,荧光介导的平台可作为一种快速(<10分钟)的替代方法,用于检测角膜真菌感染中的曲霉菌以及可能的其他真菌,以替代传统方法。