A 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.”
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.
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.