Researchers have discovered a protein named RNF114 that can reverse cataracts, which is the clouding of the eye’s lens often seen in older adults. This study, conducted on 13-lined ground squirrels and rats, could pave the way for a non-surgical method to treat cataracts, a leading cause of vision impairment.
A team from the National Institutes of Health (NIH) and their partners have pinpointed a protein called RNF114 that can reverse cataracts, a frequent condition caused by lens clouding in aging individuals. The findings from this investigation, which involved both 13-lined ground squirrels and rats, may lead to a non-invasive approach for managing cataracts, a common reason for vision loss. These results were published in the Journal of Clinical Investigation.
“Researchers have been looking for alternatives to cataract surgery, which, although effective, carries certain risks. In some regions, the inability to access cataract surgery limits healthcare options, making untreated cataracts a significant contributor to worldwide blindness,” stated Xingchao Shentu, M.D., a cataract surgeon, and co-lead investigator from Zhejiang University in China.
This groundbreaking discovery is part of ongoing research at the NIH’s National Eye Institute (NEI), which studies a mammalian hibernator, specifically the 13-lined ground squirrel. These squirrels predominantly possess cone cells in their retinas, making them ideal for examining aspects related to color vision. Additionally, their remarkable capacity to endure cold temperatures and metabolic stress during hibernation offers valuable insights for researchers studying various eye conditions.
The researchers found that when the ground squirrels hibernated, the lenses of their eyes turned cloudy at around 4 degrees Celsius but regained transparency quickly once they were warmed up. In contrast, the rat subjects, which do not hibernate, developed cataracts in cold conditions that did not clear up after rewarming.
Cataract development in these hibernating animals under cold exposure is likely a reaction of their cells to cold stress and represents one of numerous changes that occur in their bodies as they adapt to freezing temperatures and metabolic challenges. In humans, low temperatures do not trigger cataract formation.
“By understanding the molecular factors behind this reversible cataract phenomenon, we may discover possible treatment approaches,” explained co-lead investigator Wei Li, Ph.D., a senior researcher in the NEI’s Retinal Neurophysiology Section.
The primary function of the eye lens is to focus light onto the retina. Aging can lead to cataracts as proteins in the lens misfold and cluster together, obstructing, scattering, and distorting light passing through. The reason for this disruption in protein balance, known as protein homeostasis, is still unclear.
To investigate the reversible cataracts at a molecular level, the team created a laboratory model using a dish with lenses made from stem cells derived from ground squirrel cells, which were engineered in the Li Lab at NEI. This model enabled the researchers to focus on a critical part of a complex system responsible for protein homeostasis, particularly the ubiquitin proteasome system, which helps break down aged proteins.
They observed that RNF114 levels were significantly higher during the rewarming process in ground squirrels compared to non-hibernating rats. RNF114 is known to assist in identifying and degrading old proteins.
To further investigate RNF114’s impact, the researchers again used the non-hibernating rat cataract model, exposing the lenses to a chilly 4 degrees Celsius. Normally, cataracts in these lenses would not clear up after warming. However, when RNF114 was used as a pretreatment, the cataracts cleared rapidly after rewarming.
The scientific team noted that these results demonstrate the potential to induce cataract resolution in animals. In future research, they aim to refine this process to better stimulate specific protein degradation and control protein stability and turnover. This process may also play a critical role in various neurodegenerative diseases, they added.
