Lanosterol revealed clues for cataract prevention and treatment

On July 30, 2015, researchers from Sichuan University, Sun Yat-sen University, University of California, BGI, etc, reported the latest study on congenitalcataracts. The finding, published on Nature, identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.

Cataracts are the most common cause of blindness worldwide, accounting for over half of all cases of blindness worldwide. Currently the only treatment is surgical removal of cataractous lenses. High concentrations of crystallin proteins in lens fibers contribute to lens transparency and refractive properties. Protein aggregation is the single most important factor in cataract formation. Factors that lead to protein aggregation include mutations in crystallin proteins, which are known to cause congenital cataracts, or oxidative stress, which in turn contributes to age-related cataracts. However, the precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown.

Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cycliza¬tion reaction of a cholesterol synthesis pathway. Previous study showed that the specific combination of hypomorphic mutations on LSS could decrease cholesterol levels in the lens and result in cataracts in rats.

In the study, researchers identified novel homozygous mutations in the LSS gene in two consanguineous families and investigate the ability of lanosterol to alleviate protein aggregation and cataract formation. They found that, treatment by lanosterol significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. They further show that lanosterol treatment could reduce cataract severity and increase transparency in animal models.

Dr. Xin Jin, Project Leader of BGI, stated, “This project is aimed to discover casual genes for congenital cataracts. Then we uncovered that gene LSS responsible for two affected families involved in the study. This is extremely exciting when we noticed that the discovery might lead to a novel and simple strategy for the prevention and treatment of cataracts. It encourages us to have more efforts from bench to bed-side.”

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