Pharmacological Chaperone for α-crystallin Partially Restores Transparency in Cataract Models

Overview

Journal Science

Specialty Science

Date 2015 Nov 7

PMID 26542570

Citations 113

Authors

Leah N Makley

Kathryn A McMenimen

Brian T DeVree

Joshua W Goldman

Brittney N McGlasson

Ponni Rajagopal

Bryan M Dunyak

Thomas J McQuade

Andrea D Thompson

Roger Sunahara

Rachel E Klevit

Usha P Andley

Jason E Gestwicki

Affiliations

Soon will be listed here.

Abstract

Cataracts reduce vision in 50% of individuals over 70 years of age and are a common form of blindness worldwide. Cataracts are caused when damage to the major lens crystallin proteins causes their misfolding and aggregation into insoluble amyloids. Using a thermal stability assay, we identified a class of molecules that bind α-crystallins (cryAA and cryAB) and reversed their aggregation in vitro. The most promising compound improved lens transparency in the R49C cryAA and R120G cryAB mouse models of hereditary cataract. It also partially restored protein solubility in the lenses of aged mice in vivo and in human lenses ex vivo. These findings suggest an approach to treating cataracts by stabilizing α-crystallins.

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