Chemists map molecular process of cataracts

Date: Dec-06-2013A team of chemists from the US and Germany has mapped a molecular mechanism that underpins the

formation of cataracts - the world's leading cause of blindness, affecting nearly 20 million

people.

The scientists hope their groundbreaking discovery will lead to treatments that could help prevent the

condition.

"That's the dream," says one team member, Rachel Martin, associate professor of chemistry at University of

California (UC) Irvine, who describes the study - which appears on the December cover of the journal

Structure - as "a big step" and explains:

"Understanding the molecular mechanism of what goes wrong in the eye that leads to a cataract could lead to

the development of better treatment options, including more sophisticated artificial lenses and drugs."

Eye lenses have three types of crystallin protein

Scientists had already established that our lenses are able to focus while maintaining

transparency because of a delicate balance played by three kinds of crystallin protein.

Two of the proteins are structural, while a third, dubbed the "chaperone," stops the others from clumping,

which can happen if they undergo genetic mutation or become damaged by chemicals or ultraviolet light.

To try to discover which molecular mechanisms might underpin this delicate balance, the researchers explored

the structures of the normal proteins and a genetic mutation that is known to cause cataracts in young

children.

They discovered that when the mutated protein is present, chaperone proteins work extra hard to bind

strongly to the faulty protein to keep the lens transparent.

Finite supply of chaperone proteins gets used up

This sounds like a very good system, but the team discovered a major problem - the human eye does not have

an endless supply of chaperone proteins and once they are used up, the other proteins begin to aggregate
and cloud up the lens.

By mapping the molecular pathways through which these various processes happen, the team hopes organic

chemists will be able to use them as a starting point for developing ways to prevent the proteins from

clumping.

Some may wonder why this is considered so important, as there are excellent procedures now for treating

cataracts with laser surgery and other options.

But, as the World Health Organization has shown, there are millions of people who still lose their sight

through cataracts because they have no access to these corrective techniques. And these numbers are set to

escalate over the next few years, especially in India, China, Southeast Asia and the Eastern Mediterranean

regions.

Grants from the National Institutes of Health the Deutsche Forschungsgemeinschaft helped fund the study.

Earlier this year, researchers analyzing US military health care data found that statin use may raise cataract risk.

Written by Catharine Paddock PhD

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