Key Takeaways

  • Researchers at UC Irvine found that a small oxidative chemical change in a crystallin protein can make it more likely to stick to neighboring proteins, a process that may gradually cloud the eye lens

  • Understanding how age-related damage alters protein behavior could help scientists develop future treatments to slow or prevent cataracts before surgery becomes necessary

Cataracts may begin forming long before vision becomes cloudy, according to new research from the University of California, Irvine. The study reveals how a subtle chemical change in an eye lens protein can make it more likely to clump together over time—an early step that may contribute to cataract development.

The findings, published in Biophysical Reports, focus on crystallins, specialized proteins that maintain the transparency and structure of the eye lens.1 Unlike most proteins in the body, crystallins are not regularly replaced. Instead, they must remain stable and functional for a person’s entire lifetime, making them especially vulnerable to gradual chemical damage.

Researchers discovered that even a minor chemical modification to one of these proteins can increase its tendency to stick to neighboring proteins, potentially leading to the clouding of the lens that characterizes cataracts.

“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 PhD candidate in chemistry at UC Irvine. “Over time, those small interactions can add up and cloud the lens.”

The study examined age-related cataracts, the most common type of the condition. Unlike congenital or genetic cataracts, age-related cataracts typically develop slowly over decades. Environmental factors—particularly exposure to ultraviolet (UV) radiation from sunlight—can create chemical stress in the eye that gradually damages crystallin proteins. To investigate how this damage affects lens proteins, the researchers used a technique known as genetic code expansion (GCE). This method allows scientists to engineer proteins with precise chemical modifications, enabling them to recreate specific types of molecular damage found in aging tissues.

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

Using this technique, the research team introduced a small oxidative change at a single location in a lens protein known as γS-crystallin. Despite the modification, the protein remained folded and structurally stable. However, when exposed to heat stress, the altered protein clumped together far more easily than its unmodified counterpart.

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

The team is now exploring why this happens by examining how oxidation influences the natural movement of crystallin proteins. Proteins are dynamic structures that undergo subtle motions, which normally help keep fragile regions hidden from harmful interactions.

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

By linking age-related oxidation to changes in protein motion, the researchers hope to clarify how the eye’s defenses against protein aggregation weaken over time. The insights could eventually help scientists develop treatments that slow or prevent cataracts before they impair vision.

“Almost everyone who lives long enough will get age-related cataracts,” said Rachel Martin, a UC Irvine professor of chemistry and the study’s corresponding author. “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.”

The research involved several collaborators, including UC Irvine alumni Zane Long, Tsoler Demerdjian, and Acts Avenido, as well as UC Irvine professor Carter T. Butts. Experimental work was conducted in Martin’s laboratory.

The study was supported by funding from the National Institutes of Health.

Reference

Seo Y, Long ZG, Demerdjian TK, Avenido AA, Butts CT, Martin RW. Mimicking oxidative damage in γS-crystallin with site-specific incorporation of 5-hydroxytryptophan. Biophys Rep. 2026. doi:10.1016/j.bpr.2026.100004.