Pharmacological chaperone for α-crystallin partially restores transparency in cataract models

• DOI: 10.1126/science.aac9145
• Publication Date: 2015-11-05T19:19:28Z
• Authors: Leah N. Makley; Kathryn A. McMenimen; Brian T. DeVree; Joshua W. Goldman; Brittney N. McGla...; Ponni Rajagopal; Bryan M. Dunyak; Thomas J. McQuade; Andrea D. Thompson; Roger Sunahara; Rachel E. Klevit; Usha P. Andley; Jason E. Gestwicki
• Keywords: Crystallin; Chaperone (clinical); Ex vivo

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