Researchers at the University of California, Irvine have identified how a minor chemical change in an eye lens protein may contribute to the development of age-related cataracts. Cataracts are a leading cause of blindness globally and are recognized as a priority disease by the World Health Organization.
The study, published in Biophysical Reports, examines crystallins—proteins that help maintain lens clarity. Unlike most cells, the eye lens cannot replace damaged proteins, allowing chemical changes to accumulate over time.
Lead author Yeonseong (Catherine) Seo, a UC Irvine Ph.D. candidate in chemistry, explained: “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. Over time, those small interactions can add up and cloud the lens.”
The researchers focused on age-related cataracts, which typically develop gradually due to environmental factors like ultraviolet light exposure rather than genetics. UV light causes chemical stress that can damage crystallin proteins.
To investigate this process further, the team used genetic code expansion (GCE), a method that allows precise modifications of proteins. “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.”
By introducing an oxidative change at one site in γS-crystallin—a type of lens protein—the researchers found that while the modified protein remained stable under normal conditions, it clumped together more readily when exposed to heat compared with its unmodified counterpart.
“The protein doesn’t fall apart right away,” Seo noted. “It just becomes a little more likely to interact with its neighbors, and over time that can lead to clumping.”
Seo’s team is now examining how oxidation affects protein movement within the lens since subtle motions help protect vulnerable regions from exposure. “We’re essentially watching how the protein breathes,” she said. “If certain parts start moving more than they should, it can briefly open up areas that are normally protected.”
Rachel Martin, UC Irvine professor of chemistry and corresponding author on the study, commented: “Almost everyone who lives long enough will get age-related cataracts. 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.”
Other contributors included UC Irvine alumni Zane Long, Tsoler Demerdjian and Acts Avenido as well as Professor Carter T. Butts; research was conducted in Martin’s laboratory with funding from National Institutes of Health grants R01GM144964 (to C.T.B., R.W.M.) and R01EY021514 (to R.W.M.).
UC Irvine participates in NCAA Division I athletics as the Anteaters according to its official website. The university has earned recognition for very high research activity through Carnegie classification (source) and operates within the University of California system (source). UC Irvine emphasizes advancing knowledge through research and public service focused on inclusive excellence (source), maintains accreditation from WASC Senior College and University Commission (source), and engages in international collaborations (source).
