Setting the Biological Clock

A switching mechanism in the eye plays a key role in regulating the sleep and wake cycles in mammals, UVA biologists have found.

Light receptor cells in the eye are central to setting the rhythms of the brain’s primary timekeeper, the suprachiasmatic nuclei, which regulates activity and rest cycles. “The finding is significant because it changes our understanding of how light input from the eye can affect activity and sleep patterns,” says Susan Doyle, the study’s lead investigator. The findings were recently published in the Proceedings of the National Academy of Sciences.

Researchers discovered that they could reverse the temporal niche of mice—in other words, they were able to switch the animals’ activity phase from their normal night activity to being diurnal, or day active. They accomplished this by reducing the intensity of light given to normal mice and by creating a mutated line of mice with reduced light sensitivity in their eyes. The mutated mice were fully active in the day but inactive at night, a complete reversal of their usual cycle.

“The significance of this research for humans is that it could ultimately lead to new treatments for sleep disorders, perhaps even eye drops that would target neural pathways to the brain’s central timekeeper,” says Doyle.

Biological clocks are the body’s complex network of internal oscillators that regulate daily activity and rest cycles and other important aspects of physiology, including body temperature, heart rate and food intake. In addition to sleep disorders, research in this field may eventually help treat the negative effects of shift work, aging and jet lag.

As the U.S. population ages, a growing number of people are developing visual impairments that can result in sleep disorders. “Currently, one in 28 Americans age 40 and over suffer from blindness or low vision, and this number is estimated to double in the next 15 years,” Doyle says. “Our discovery of the switching mechanism in the eye has direct relevance with respect to the eventual development of therapies to treat circadian and sleep disorders in the visually impaired.”