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New & Now: Fall 2008

Darkness Visible

Trains on Time

Vision Quest

Plastic War

Disappearing Doctors

Bad Business

Early Warning

Protective Paste

 

Vision Quest

Peptides a key to cataract onset.

Charles Darwin marveled at the "absurd" complexity of the human eye, devoting three densely written pages of The Origin of Species to speculations on its evolutionary provenance.

Today's scientists, thanks to a century of investigation, are better equipped to explain the eye's fantastically attenuated functionality. But even now they don't have all the answers.

One of the most vexing unknowns involves cataracts, masses of proteins that cloud the vision of millions of mostly elderly Americans.

Healthy eyes, explains K. Krishna Sharma, a professor of ophthalmology at MU, use a lens comprised of proteins and water to focus light onto the retina. Some 90 percent of these proteins take the form of crystallins, structures that maintain lens clarity by "chaperoning" potentially light-blocking molecules away from the lens surface. These crystallins themselves break down over time, becoming peptides that must also be cleared from the eye.

As the eye ages, broken-down crystallins form at an accelerated rate, increasing the number of small peptides in the eye. Chaperoning activity, meanwhile, begins to slow. When chaperoning can no longer keep up, peptides and proteins clump together and cataracts form, clouding the lens and obstructing or blurring retinal images. "It's a very sad situation, because cataracts can have a huge impact on the quality of a person's life," Sharma says.

Thankfully, researchers are fast unraveling the molecular foundations of cataract formation, progress that may lead to new methods for preventing them. In a study published earlier this year in the Journal of Biological Chemistry, Sharma, working with a team of MU ophthalmologists and biochemists, used a mass spectrometer to identify 23 peptides in donor lenses from young, old and cataract-affected eyes. After a series of cross comparisons, they isolated two peptides that appeared only in the aged and cataract-affected lenses. Further study suggested that interaction among these peptides and intact crystallins could signal the onset of cataracts.

"It is very helpful to track the formation of these peptides. The next step is to work on preventing their formation," says Sharma.

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Published by the Office of Research.

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