UC Irvine chemists shed light on how age-related cataracts may begin

(Press-News.org) Irvine, Calif., March 4, 2026 — Cataracts are a leading cause of blindness worldwide and are considered a priority disease by the World Health Organization. In a new study, researchers at the University of California, Irvine uncovered how a subtle chemical change in an eye lens protein can make the protein more likely to clump together over time, suggesting an early step in cataract formation.

The research, published in Biophysical Reports, focuses on proteins called crystallins, which help keep the eye lens clear. These proteins are meant to last a lifetime. But unlike most cells in the body, the lens cannot replace damaged proteins, so chemical changes can gradually accumulate over decades.

“What surprised us is that the protein can still look mostly normal, but even a small chemical change makes it much more likely to stick to other proteins,” said lead author Yeonseong (Catherine) Seo, a UC Irvine Ph.D. candidate in chemistry. “Over time, those small interactions can add up and cloud the lens.”

The team studied age-related cataracts, the most common form of the disease. Rather than being caused by genetics, this type typically develops slowly due to environmental exposure, such as ultraviolet light from the sun. UV light creates chemical stress in the eye that can damage crystallin proteins.

To better understand how this damage affects lens proteins, the researchers turned to a tool called genetic code expansion, or GCE. This method allows scientists to build proteins with specific chemical features.

In their study, Seo and her team used the tool differently to recreate a single type of chemical change that naturally occurs in the aging eye.

“GCE lets us make very precise changes to a protein,” Seo said. “We used it to copy one kind of damage that shows up in age-related cataracts and see exactly what it does.”

Using this approach, the researchers introduced a small oxidative change at one specific location in a lens protein called γS-crystallin. Even with this modification, the protein remained folded and stable. But when stressed by heat, it clumped together much more easily than the unmodified version.

“The protein doesn’t fall apart right away,” Seo explained. “It just becomes a little more likely to interact with its neighbors, and over time that can lead to clumping.”

Seo and her team are now investigating why this happens by studying how oxidation affects the natural movement of these proteins. Proteins are not rigid structures, and their subtle motions help keep vulnerable regions safely tucked away.

“We’re essentially watching how the protein breathes,” said Seo. “If certain parts start moving more than they should, it can briefly open up areas that are normally protected.”

By connecting age-related oxidation to changes in protein motion, the researchers hope to better understand how the eye’s natural defenses against protein clumping gradually weaken with age. This work moves researchers one step closer to finding ways to slow or prevent cataracts before it affects vision.

“Almost everyone who lives long enough will get age-related cataracts,” said Rachel Martin, UC Irvine professor of chemistry and corresponding author on the study. “GCE enables us to study specific changes that happen with proteins in the aging lens, furthering our understanding of what causes cataracts at the molecular level. Understanding the loss of function that comes with aging could lead to non-surgical treatments or improved artificial lenses in the future.”

Key collaborators include UC Irvine alumni Zane Long, Tsoler Demerdjian, Acts Avenido, and UC Irvine Professor Carter T. Butts. The experimental work was performed in the lab of Rachel W. Martin. Key sources of funding include the National Institutes of Health under award numbers R01GM144964 to C.T.B. and R.W.M. and R01EY021514 to R.W.M.

About the University of California, Irvine: Founded in 1965, UC Irvine is a member of the prestigious Association of American Universities and is ranked among the nation’s top 10 public universities by U.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UC Irvine has more than 36,000 students and offers 224 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide. For more on UC Irvine, visit www.uci.edu.

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