Cataract Removal Without Surgery, From the Secret of a Squirrel Possible Drug

Thirteen-striped ground squirrels have a secret: When they hibernate, their eye lenses become opaque at 4 degrees, then quickly return to transparency when they warm up and their temperature rises. This ability could also be useful to humans. The ability to make the lens opaque is in fact precisely what could be useful in the case of cataracts. And by studying these hibernating rodents, a group of researchers led by the National Institutes of Health (NIH) has identified a key protein in this process, known as RNF114, which reverses cataracts.

Cataracts are a clouding of the lens of the eye that commonly occurs in people as they age. The study in 13-striped ground squirrels and rats could represent a possible strategy for treating them without surgery, making it easier to combat a common cause of vision loss. Surgery is “effective, but not without risks,” and “scientists have long sought an alternative” to the “scalpel,” says Xingchao Shentu, a cataract surgeon and co-principal investigator at Zhejiang University in China. Also because, he points out, “in some parts of the world, lack of access to cataract surgery is a barrier to treatment, and this makes untreated cataracts a leading cause of blindness worldwide.”

The study was published in the ‘Journal of Clinical Investigation’ and describes this new discovery obtained in the context of ongoing research at the National Eye Institute (NEI), a center of the NIH, conducted involving the 13-striped ground squirrel. In this animal, the photoreceptor cells sensitive to light in the retina are mostly cones, which makes it useful for studying properties such as color vision. In addition, the rodent’s ability to withstand months of cold and metabolic stress during hibernation makes it a model for vision scientists to study a variety of eye diseases. The ability to make the lens opaqueness reversible was observed in the squirrels involved in the study, while in rats (a non-hibernating species) it was not. The latter developed cataracts at low temperatures, which did not resolve with warming.

Cataract formation in hibernating animals exposed to cold temperatures, experts note, is likely a cellular response to cold stress and is one of many changes their bodies undergo as tissues adapt to freezing temperatures and metabolic stress. Humans do not develop cataracts when exposed to cold temperatures. “Understanding the molecular drivers of this reversible cataract phenomenon could point us in the direction of a potential treatment strategy,” says study co-principal investigator Wei Li, a senior researcher in the retinal neurophysiology section at NEI.

As we age, cataracts form when proteins in the lens of the eye begin to misfold and form clusters that block, scatter, and distort light as it passes through the lens. To explore the ground squirrel’s reversible cataracts at the molecular level, the team developed a model lens in the lab using stem cells engineered from squirrel cells. Using this platform, the researchers found that the protein RNF114 was significantly elevated during warming in the ground squirrel, compared to the non-hibernating rat. Previously, it had been shown that RNF114 helped identify old proteins and facilitate their degradation. Indeed, when the scientists pretreated the lens models with the protein, the cataracts disappeared rapidly upon warming.

These findings, they note, are proof of principle that it is possible to induce cataract removal in animals. In future studies, the process will have to be refined. But this mechanism is considered promising, and, the authors note, it is also an important factor in many neurodegenerative diseases.