Cataracts are the 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 have revealed how subtle chemical changes in the eye’s lens proteins make them more likely to clump together over time, suggesting the early stages of cataract formation.
This study biophysical reportfocuses on proteins called crystallins, which help keep the eye’s lens clear. These proteins last a lifetime. But unlike most cells in the body, the lens cannot replace damaged proteins, so chemical changes can accumulate gradually over decades.
What surprised us was that even small chemical changes made the protein much more likely to attach to other proteins, even though the protein still looked mostly normal. Over time, these small interactions can add up and cloud the lens. ”
Yong-Sung (Catherine) Seo, PhD candidate in chemistry, University of California, Irvine, first author
The research team studied the most common disease, age-related cataracts. This type is not caused by genetics and usually develops slowly due to environmental exposure, such as ultraviolet radiation from the sun. UV rays can cause chemical stress in the eyes and damage crystallin proteins.
To better understand how this damage affects lens proteins, researchers turned to a tool called genetic code expansion (GCE). This method allows scientists to build proteins with specific chemical characteristics.
In the study, Seo and her team used this tool in a different way to recreate one type of chemical change that naturally occurs in aging eyes.
“GCE allows us to make very precise changes to proteins,” Seo says. “We used this to copy the type of damage that appears in age-related cataracts and see exactly what effect it has.”
Using this approach, the researchers introduced small oxidative changes at specific locations in a lens protein called γS-crystallin. Even with this modification, the protein remained folded and stable. However, when subjected to heat stress, it aggregated much more easily than the unmodified version.
“Proteins don’t break down quickly,” Seo explains. “Even just a little bit more chance of interacting with the animals next door can cause clumps to form over time.”
Soh 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 movements allow them to safely hide vulnerable areas.
“We’re basically looking at how proteins breathe,” Seo says. “If certain parts start moving more than they should, areas that are normally protected can temporarily open up.”
By linking age-related oxidation to changes in protein movement, the researchers hope to better understand how the eye’s natural defenses against protein aggregation gradually weaken with age. This study brings researchers one step closer to finding ways to slow or prevent cataracts before they affect vision.
“If we live long enough, almost everyone will develop age-related cataracts,” said Rachel Martin, a chemistry professor at the University of California, Irvine and corresponding author of the study. “GCE allows us to study the specific changes that occur in proteins in the aging lens, increasing our understanding at the molecular level of the causes of cataracts. Understanding age-related loss of function may lead to improved non-surgical treatments and artificial lenses in the future.”
Key collaborators include UC Irvine alumni Zane Long, Zoller Demerjian, and Act Avenido, and UC Irvine Professor Carter T. Butts. Experimental work was performed in Rachel W. Martin’s laboratory. Primary funding sources include the National Institutes of Health with award number R01GM144964 to CTB and RWM and award number R01EY021514 to RWM.
sauce:
University of California, Irvine
Reference magazines:
Seo, Y. others. (2026). Site-specific incorporation of 5-hydroxytryptophan mimics oxidative damage to γS-crystallin. Biophysical report. DOI: 10.1016/j.bpr.2026.100251. https://www.cell.com/biophysreports/fulltext/S2667-0747(26)00004-2
