Learning how hibernating ground squirrels curtail cataracts and survive deep-freeze

2024

Challenge

Cloudy spaces in the eye’s lens, known as cataracts, are a leading cause of blindness worldwide. While surgery can be a successful treatment, scientists are also investigating non-surgical solutions to cataracts. Hibernating mammals, which can survive extreme conditions such as near-freezing body temperatures without damaging their cells or tissues, provide an opportunity to study a variety of health challenges, including — unexpectedly — how to reverse cataracts.

Advance

NIH researchers led by IRP senior investigator Wei Li, Ph.D., observed that ground squirrels develop cataract-like cloudy areas in the lenses of their eyes when hibernating; however, these cataracts quickly cleared when the animals came out of hibernation. What’s more, the scientists discovered that when the squirrels came out of hibernation, their eyes had higher levels of a molecule that helps to clear abnormal protein aggregations in the lens. Interestingly, administering this molecule to animals with cataracts can also clear their lens. Additional experiments revealed that the squirrels’ cold tolerance is related to a process that moves a protein called FOXO1 into the nuclei of cells during hibernation, resulting in changes in how certain genes behave.

Impact

Understanding the molecular mechanisms that enable hibernators to survive life-threatening conditions holds significant potential for medicine, as we may be able to mimic these hibernating strategies to address important human health concerns. Specifically, the IRP scientists’ findings reveal molecular mechanisms that could lead to non-surgical treatments for cataracts. In addition, the results suggest that drugs that cause FOXO1 to stay in the cell nucleus could enhance the cold tolerance of cells, thereby addressing a critical need in the field of organ transplantation by significantly extending the time that tissues and organs can be stored without degrading.

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