Rosmarinic acid restores complete transparency of sonicated human cataract ex vivo and delays cataract formation in vivo

Marina Chemerovski-Glikman, Michael Mimouni, Yarden Dagan, Esraa Haj, Igor Vainer, Raviv Allon, Eytan Z. Blumenthal, Lihi Adler-Abramovich, Daniel Segal, Ehud Gazit, Shiri Zayit-Soudry

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish
Article number9341
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 19 Jun 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

Funding

We would like to thank Prof. Maya Schuldiner for the discussion of the activity of 25-hydroxycholesterol and for providing us with the compound. We are also thankful to the Gazit and Segal lab-teams for the comprehensive and fruitful discussions. This research work is supported by the Rambam-Atidim Academic Excellence Program and generously supported by a grant from The Edna & Jonathan Sohnis Clinical Scientific Research Fund.

FundersFunder number
Edna & Jonathan Sohnis Clinical Scientific Research Fund

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