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Washington, D.C., September 19, 2024 — Researchers at the National Institutes of Health (NIH) and their international collaborators have identified a promising new approach for managing cataracts, a prevalent cause of vision loss. Published in the Journal of Clinical Investigation, the study highlights the role of a protein called RNF114 in reversing cataract formation, potentially offering a non-surgical alternative to traditional treatments.
Cataracts, characterized by the clouding of the eye’s lens, commonly occur as people age and are a leading cause of blindness worldwide. While cataract surgery remains effective, it is not universally accessible, particularly in underserved regions. This new research could pave the way for a breakthrough in treatment options, addressing a critical barrier to care.
The study, conducted by NIH’s National Eye Institute (NEI) in collaboration with Zhejiang University in China, used the 13-lined ground squirrel—a mammalian hibernator—as a model. Ground squirrels are particularly useful for studying vision due to their unique retinal properties and ability to withstand extreme temperatures during hibernation.
Researchers discovered that during hibernation, the ground squirrel’s lenses become cloudy at around 4 degrees Celsius but regain transparency upon rewarming. In contrast, non-hibernating rats exposed to the same conditions developed cataracts that did not resolve with rewarming.
“This reversible cataract phenomenon in hibernating animals is likely a cellular response to cold stress,” said Wei Li, Ph.D., co-lead investigator and senior investigator in the NEI Retinal Neurophysiology Section. “Understanding the molecular drivers of this process could guide us toward potential treatment strategies.”
The team focused on the molecular mechanisms involved in this reversible cataract formation. They developed a lens-in-a-dish model using stem cells from ground squirrels to study the underlying processes. Their research identified RNF114 as a crucial protein involved in maintaining protein homeostasis by targeting and degrading old proteins. Elevated levels of RNF114 were observed during rewarming in ground squirrels, compared to non-hibernating rats.
In further experiments, the researchers treated rat cataract models with RNF114, which led to a significant clearing of cataracts upon rewarming. This proof-of-principle suggests that RNF114 or similar interventions could potentially be used to induce cataract clearance in humans.
“These findings are a significant step forward in demonstrating that cataract clearance is achievable through molecular interventions,” said Xingchao Shentu, M.D., cataract surgeon and co-lead investigator from Zhejiang University. “Future studies will need to refine these methods to target specific proteins and regulate their stability and turnover.”
The research was supported by the NEI Intramural Research Program and represents a collaborative effort with Zhejiang University. Further studies are anticipated to explore how this mechanism can be applied to human cataract treatment, potentially offering a groundbreaking, non-surgical solution for this widespread condition.
For more information, refer to the study in the Journal of Clinical Investigation: Yang, H., et al. (2024). Reversible cold-induced lens opacity in a hibernator reveals a molecular target for treating cataracts. Journal of Clinical Investigation. doi.org/10.1172/JCI169666.
Source: NIH/National Eye Institute
