NIH-Led Studies Point to Potential for New Cataract Drug

Photo:  PEOPLEIMAGES-YURI A/SHUTTERSTOCK

NIH researchers and collaborators have identified a protein, known as RNF114, that reverses cataracts, a clouding of the eye’s lens that occurs commonly in people as they age. The study may represent a surgery-free strategy for managing the condition. The study was published in the Journal of Clinical Investigation.

This new discovery was part of ongoing research at NEI involving the 13-lined ground squirrel. Its ability to withstand months of cold and metabolic stress during hibernation make it an ideal model for vision scientists to study a range of eye diseases.

During hibernation, the ground squirrel’s lenses became cloudy at around 4 degrees Celsius but quickly turned transparent after rewarming. By comparison, non-hibernators (rats in this study) developed cataracts at low temperatures that did not resolve with rewarming.  

The lens focuses light onto the retina at the back of the eye. As we age, cataracts form when proteins in the lens start misfolding and block, scatter and distort light as it passes through the lens. Aging can disrupt protein homeostasis. One previously known role of RNF114 is to help identify old proteins and facilitate their degradation.

The researchers developed a lens-in-a-dish model using stem cells engineered from ground squirrel cells to explore the squirrel’s reversible cataracts at a molecular level. They found RNF114 was significantly elevated during rewarming in the ground squirrel, but not in the non-hibernating rat.

They compared these results with a rat cataract model that had been pre-treated with RNF114. Normally, such cataracts would not resolve with rewarming, but in the pre-treated lenses 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. The process will need to be fine-tuned so scientists can stimulate specific protein degradation to see how to precisely regulate protein homeostasis. This mechanism is also an important factor in many neurodegenerative diseases.