Cataract removal is one of the oldest and most common surgeries in the world. A surgeon makes small incisions in the eye, sucks out the cloudy lens and replaces it with an artificial lens implant. Complications are rare but can range from blurred vision and light sensitivity to retinal detachment, which can lead to blindness if untreated.
By studying the hibernation of a small ground squirrel, researchers from the NIH’s National Eye Institute (NEI) and collaborators in China have identified a protein that may be able to get rid of cataracts without the need for surgery. The results were published in the Journal of Clinical Investigation on Sept. 17.
“Scientists have long searched for an alternative to cataract surgery, which is effective, but not without risk,” Xingchao Shentu, M.D., a cataract surgeon at Zhejiang University in China, said in a press release. “Lack of access to cataract surgery is a barrier to care in some parts of the world, causing untreated cataracts to be a leading cause of blindness worldwide.”
The thirteen-lined ground squirrel lives in grassy areas across North America. They’ve become an increasingly popular model organism for studying adaptations to stress because of their ability to withstand frigid temperatures when they hibernate over the winter.
Shentu and colleagues noticed that during hibernation, at around 39 degrees Fahrenheit, the squirrels developed cloudy spots in their eyes. Once they warmed back up, their lenses cleared up.
When non-hibernating rodents like rats and mice were chilled, their lenses got cloudy too, but took much longer to clear up with warmth. The researchers suspected that the squirrels’ reversible cataract-like cloudiness might be an adaptation to cold stress.
To identify how hibernating squirrels pull this off, the researchers analyzed the proteomes of lenses from thirteen-lined ground squirrels and rats and saw that the squirrel cells had more activity in the ubiquitin-proteasome system (UPS). The UPS is a waste disposal system for proteins that are no longer needed in the cell.
The researchers then took stem cells from the squirrels and induced them to become lens cells, creating a sort of “lens in a dish.” They chilled and rewarmed the cells and isolated crystallin proteins, which are responsible for accumulating and causing cataracts. Attached to the crystallin was RNF114, a protein known to have protein-degradation activity in the ubiquitin pathway.
To see if RNF114 could be used to treat cataracts, they treated rat lenses with the protein and then cooled them down to give them cataracts. Pre-treatment with RNF114 gave the rat lenses the same cataract-reversing power seen naturally in the ground squirrels. In a follow-up experiment with zebrafish, the molecule again could clear up cataracts, with treated fish regaining clearer vision within 12 hours.
“Understanding the molecular drivers of this reversible cataract phenomenon might point us in a direction toward a potential treatment strategy,” Wei Li, Ph.D., a neurophysiologist at the NEI and co-author of the study, said in the release.