Research in rats and hibernating squirrels has pinpointed a naturally occurring protein that appears to reverse cataracts, scientists report.

Animal studies don’t always pan out in people, of course. But the discovery of the RNF114 protein raises the possibility of surgery-free cataract removal, according to a team from the U.S. National Eye Institute (NEI).

“Understanding the molecular drivers of this reversible cataract phenomenon might point us in a direction toward a potential treatment strategy,” said the study’s co-lead investigator, Wei Li. He’s a senior investigator in the NEI’s Retinal Neurophysiology Section.

His team published its findings Sept. 17 in the Journal of Clinical Investigation.

As the NEI explained, “a cataract is a cloudy area in the lens of your eye [the clear part of the eye that helps to focus light]. This can make your vision cloudy.”

Right now, surgery is a patient’s only treatment option, and almost 4 million such procedures are conducted in the United States each year.

A non-surgical approach has long been a holy grail of ophthalmological research.

Meanwhile, anyone living in the American heartland has probably seen a 13-lined ground squirrel.

These hardy creatures are perfect for cataract research, Li’s team explained, because their retinas contain light-sensitive photoreceptor cells that are mostly cones, not the “rods and cones” found in the human eye. Cones are especially tied to color vision.

These prairie squirrels can also withstand the rigors of a long hibernation each year.

Li’s team found that the lenses of the squirrels’ eyes turned cloudy at around 39 degrees Fahrenheit — indicative of cataract — but then quickly reversed that process to become transparent again after rewarming.

Another creature, the lab rat, developed cataracts at the same low temperatures, but those cataracts remained permanent.

Cataract formation occurs in many species (but not humans) when cold temperatures strike, as an adaptation to metabolic stress, the researchers explained.

So, how does the 13-lined ground squirrel reverse its winter-clouded vision in the spring? The answer lies in how cataracts form to begin with.

Cataracts form with age in people, as “proteins in the lens start mis-folding and forming clusters that block, scatter and distort light as it passes through the lens,” according to an NEI news release.

Cataracts become more common with age because, for reasons that aren’t clear, age degrades the healthy turnover of proteins and cells within the eye.

In detailed work in the lab, Li and colleagues first collected stem cells derived from the ground squirrels. Investigating further, they isolated the RNF114 protein as being crucial to healthy protein turnover in the animals’ eyes.

“RNF114 was significantly elevated [in the eye] during rewarming in the ground squirrel,” the NEI researchers said. That wasn’t true for rats placed in the same setting.

However, when the scientists injected extra RNF114 into the eyes of rats with cataracts, they observed a rapid reversal of the rodents’ cataracts, similar to what happened with the squirrels.

This strongly suggests that mammals with cataracts besides the ground squirrel might benefit from a bumped-up dose of RNF114 after cataracts form.

That list of mammals might someday include people, the team believes.

“Scientists have long searched for an alternative to cataract surgery, which is effective, but not without risk. 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,”  said study co-lead author Dr. Xingchao Shentu, a cataract surgeon and researcher at Zhejiang University, in China.

More information

Find out more about cataracts at the American Academy of Ophthalmology.

SOURCE: U.S. National Eye Institute, news release, Sept. 18, 2024

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