Scientists in the United States have found a protein that has potential to reverse cataracts, opening the possibility of surgery-free treatments for managing cataract.

The protein, RNF114, was discovered as part of ongoing research at the National Eye Institute (NEI) in the United States involving a mammalian hibernator, the 13-lined ground squirrel.

Researchers learned that during hibernation, the ground squirrel’s lenses became cloudy at around 4°C but quickly turned transparent after rewarming. By comparison, non-hibernating rats developed cataracts at low temperatures, but they did not resolve with rewarming.

Cataract formation in hibernating animals exposed to low temperatures is likely a cellular response to cold stress (humans do not develop cataracts when exposed to low temperatures).

SQUIRREL LENS-IN-A-DISH

To explore the ground squirrel’s reversible cataracts at the molecular level, the team developed a ‘lens-in-a-dish’ model using squirrel stem cells. Using this platform, they discovered the protein RNF114 was significantly elevated during rewarming in the ground squirrel, compared with the non-hibernating rat.

To look further at RNF114’s effect, they again used a non-hibernator (rat) cataract model by incubating its lenses at 4°C. Normally, such cataracts would not resolve with rewarming. However, when the lenses were pretreated with RNF114, there was a rapid clearing of the cataract upon rewarming.

According to the scientific team, these findings are proof-of-principle that it is possible to induce cataract clearance in animals.

“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, Dr Wei Li, from NEI.

Co-lead investigator and cataract surgeon, Dr Xingchao Shentu, from Zheiang University in China said, “scientists have long searched for an alternative to cataract surgery, which is effective, but not without risk”.

The study was published in the Journal of Clinical Investigation.1

Reference
1. Yang H, Ping X, Shentu X, et al. Reversible cold-induced lens opacity in a hibernator reveals a molecular target for treating cataracts. JCI, published online 17 Sept 2024. doi: 10.1172/ JCI169666.