• Cataract/Anterior Segment, Comprehensive Ophthalmology

    In what could be a game changer in cataract treatment, researchers at the University of California, San Francisco have identified a steroid that has the potential to reverse cataracts by blocking α-crystallin aggregation.

    The research exploits a crucial difference between properly folded crystallins and their amyloid forms that generate cloudiness in the lens: their melting point. The researchers hypothesized that compounds that reduce the melting point of mutant crystallin could potentially increase protein solubility and decrease clumping and amyloid formation.

    Using differential scanning fluorimetry, which allowed the scientists to measure the temperature at which a target protein begins to melt, they determined the mutant protein had a melting point 4 degrees higher than the wild-type protein. The team then focused on finding chemicals that that lowered the melting point of crystallin amyloids to the normal, healthy range.

    Beginning with 2,450 compounds, they eventually identified 1 that most effectively decreased the melting temperature of mutant crystallins, compound 29. Compound 29 is a member of a chemical class known as sterols. Using electron microscopy, nuclear magnetic resonance and solubility tests, they showed that compound 29 could block amyloid formation and partially reverse mutant crystallin insolubility in vitro.

    Additionally, they found that a single drop of compound 29 administered 3 times a week for 2 weeks significantly improved lens opacity by an average of one grade (LOCS III) in mouse models that had age-related or hereditary cataract. These effects were evident 4 weeks after treatment stopped. The authors also performed ex vivo studies using human lens material from patients with cataract and found that compound 29 increased the soluble protein content by 18%.

    This is the second study this year to show that sterols can potentially reverse cataracts. A study published in the July 2015 issue of Nature showed that lanosterol production is halted in children with congenital cataract, and that lanosterol injections reduced cataract severity in dogs. Both studies suggest the possibility of a  future non-surgical treatment of cataract.