imprint:
Springer Science and Business Media LLC, 2018
Published in:Scientific Reports
Language:
English
DOI:
10.1038/s41598-018-27516-9
ISSN:
2045-2322
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>ex vivo</jats:italic> 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 <jats:italic>ex vivo</jats:italic>. Mechanistic studies demonstrated that both compounds reduce cataract microparticle size and modify their amyloid-like features. <jats:italic>In vivo</jats:italic> studies confirmed that the lead compound, rosmarinic acid, delays cataract formation and reduces the severity of lens opacification in model rats. Thus, the <jats:italic>ex vivo</jats:italic> assay may provide an initial platform for broad screening of potential novel therapeutic agents towards pharmacological treatment of cataract.</jats:p>