Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, 69978, Israel.
Department of Ophthalmology, Rambam Health Care Campus, Technion Israel Institute of Technology, Haifa, Israel.
Sci Rep. 2018 Jun 19;8(1):9341. doi: 10.1038/s41598-018-27516-9.
Cataract, the leading cause of vision impairment worldwide, arises from abnormal aggregation of crystallin lens proteins. Presently, surgical removal is the only therapeutic approach. Recent findings have triggered renewed interest in development of non-surgical treatment alternatives. However, emerging treatments are yet to achieve full and consistent lens clearance. Here, the first ex vivo assay to screen for drug candidates that reduce human lenticular protein aggregation was developed. This assay allowed the identification of two leading compounds as facilitating the restoration of nearly-complete transparency of phacoemulsified cataractous preparation ex vivo. Mechanistic studies demonstrated that both compounds reduce cataract microparticle size and modify their amyloid-like features. In vivo studies confirmed that the lead compound, rosmarinic acid, delays cataract formation and reduces the severity of lens opacification in model rats. Thus, the ex vivo assay may provide an initial platform for broad screening of potential novel therapeutic agents towards pharmacological treatment of cataract.
白内障是全球导致视力损害的主要原因，它源于晶状体蛋白的异常聚集。目前，手术切除是唯一的治疗方法。最近的发现引发了人们对开发非手术治疗替代方法的新兴趣。然而，新兴的治疗方法尚未实现完全和一致的晶状体清除。在这里，开发了第一个用于筛选可减少人晶状体蛋白聚集的药物候选物的体外筛选检测方法。该检测方法鉴定出两种主要化合物可促进体外乳化白内障制备物的几乎完全透明的恢复。机制研究表明，这两种化合物都可以减小白内障微颗粒的大小并改变其类淀粉样特征。体内研究证实，先导化合物迷迭香酸可延迟模型大鼠白内障的形成并降低晶状体混浊的严重程度。因此，该体外检测方法可能为广泛筛选潜在的新型治疗剂以用于白内障的药理学治疗提供了一个初始平台。
