NIH Studies Suggest Potential for New Cataract Drug Development

Press release

Wednesday, September 18, 2024

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Animal studies suggest that cataract surgery can be avoided.

The National Institutes of Health and its collaborators have identified a protein, RNF114, that reverses cataracts that occur in the lens of the eyes with age. This study was conducted on rats and chipmunk squirrels. This may be a way to manage cataracts without surgery. This study was published in The Journal of Clinical Investigation.

Scientists are looking for an effective alternative to cataract surgery that is not without risks. In some countries, the lack of access to cataract surgery makes providing care difficult. Untreated cataracts are a major cause of blindness.

The striped ground squirrel was a hibernating mammal that is the subject of research at the NIH's National Eye Institute. The retina of these ground squirrels is dominated by cones. This makes them a good model for studying cone-related phenomena, such as color vision. The squirrel is also a model to help vision scientists study eye disorders because of its ability to endure months of cold during hibernation and manage metabolic stress.

The researchers found that the ground squirrels' lenses became opaque at temperatures around 4 degrees Celsius during hibernation. However, they quickly returned to their original transparency after warming up. In contrast, the rats in the study that were not hibernators developed cataracts when temperatures dropped below 4 degrees Celsius, and they did not disappear after warming up.

Cataract formation in animals hibernating at low temperatures may be a cellular response to the cold. It's just one of the changes their bodies undergo as they adapt their tissues to the frigid temperatures and metabolic stress. When exposed to cold temperatures, humans do not develop cataracts.

Wei Li Ph.D. is the co-principal investigator of the study and a senior researcher in the Retinal Neurophysiology Section at NEI.

The lenses are responsible for focusing light onto the retina, located at the back of the eye. As we age, the lenses develop cataracts when proteins begin to fold incorrectly and form clumps that block, scatter, and distort the light passing through them. Aging can disrupt protein homeostasis for unknown reasons. This is a process that maintains a balance between newly produced proteins and old proteins.

The team used stem cells engineered by the Li lab at NEI to explore ground squirrels' reversible crystallins at the molecular level. The researchers used this platform to focus on the ubiquitin-proteasome system, a cellular network that helps maintain protein homeostasis by breaking down old and damaged proteins.

RNF114, in particular, increased significantly during warming in ground squirrels compared to non-hibernating rats. RNF114 has previously been shown to be able to identify and degrade old proteins.

To examine the effect of RNF114, the researchers used another non-hibernating rat cataract model and incubated its lenses at 4° Celsius. These cataracts do not normally disappear with warming. When the lenses were pretreated with RNF114 solution, the cataracts disappeared quickly after warming.

The scientific team believes these results are proof of principle showing that it is possible to reverse cataracts in animals. The process needs to be refined in future research so that scientists can precisely control protein turnover and stability. They stated that this mechanism plays a role in several neurodegenerative disorders.

Researchers from Zhejiang University in Hangzhou, China, conducted the research with support from the NEI Intramural Research Program.

Visit the website for more information. National Eye Institute on Cataracts website.

The NEI leads the federal government in its efforts to eradicate vision loss and improve quality of life through vision research. It does this by stimulating innovation, fostering cooperation, increasing the number and diversity in the field, and educating key stakeholders and the public. The NEI funds basic and clinical research programs that aim to improve the quality of life of people with low vision and develop sight-saving treatments. Visit for more information. https://www.nei.nih.gov.

The National Institutes of Health: The NIH is the medical research agency of the U.S. Department of Health and Human Services. It comprises 27 institutes and centers. The NIH, the nation's medical research agency, is the primary federal agency conducting and supporting basic, translational, and clinical medical research. It also studies the causes, treatments, and cures for common and rare diseases. Visit the NIH for more information about its programs. www.nih.gov.

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