Originally created 02/12/02

Discovery of eye cell sheds light on biological clock



Scientists have discovered a new type of specialized, light-sensing cell in the eye that keeps the brain's built-in circadian clock running on track.

The new findings outline a previously unknown link between basic physiology and the amount of light in the environment, suggesting a new approach for relieving jet lag, the grind of shift work and maybe even the wintertime blues.

It's long been clear that the amount of light in the environment has a big effect on hormones, mood and many other basic body functions. But how light cues are gathered and sent to the brain is only now starting to become clear.

"What we've found here is a novel apparatus in the eye to detect light," said neuroscientist Ignacio Provencio, an assistant professor at the Uniformed Services University of the Health Sciences in Bethesda, Md.

The spidery cells and a photopigment within them, known as melanopsin, link into "a photoreceptive net in the retina," Provencio said, sending critical signals for the brain to fulfill its role as the body's pacemaker.

Five independent labs in the United States and Europe, including Provencio's, have weighed in recently with molecular and anatomic details of this new class of retinal photoreceptors. The latest findings appeared Friday in a pair of research reports, along with a related summary article, in the journal Science.

"These cells seem to be specialized to encode the amount of light energy entering the eye, and pretty much that's it," said David Berson, a physiologist at Brown University and a lead author of one of Friday's reports.

Despite 150 years of close study of the visual system, this parallel system of light detection stayed hidden until about five years ago, and direct evidence in humans is still proving elusive.

Unlike the visual system, designed to be exquisitely sensitive even in the dimmest starlight, the circadian light-relay system seems geared to the subtle, slow-changing rhythms of the sun and seasons.

"You wouldn't want things like a bright moonlit night, or maybe a bolt of lightning, to reset your internal clock," Provencio noted.

The recent spate of findings stem in part from the puzzling discovery in the mid-1990s that blind people, with no functional visual system capable of detecting light in the usual manner, were still capable of resetting their circadian clocks with a shift in day-night cycles.

Early experiments in animals also produced evidence that the familiar rods and cones could not be the only way the brain picks up how much light is hitting the eyes.

Provencio and colleagues determined that melanopsin was the critical messenger, finding it first in the photosensitive skin of amphibians, later in the eyes of mammals. Cloning experiments confirmed the same protein is produced in humans.

In the experiments reported Friday, Berson and his associates describe for the first time how the brain's clock region connects to the specialized light sensors, known as "intrinsically light-sensitive retinal ganglion cells."

The critical signals go directly to an area deep within the brain known as the suprachiasmatic nucleus, or SCN, long known to help regulate mood and alertness.

The sensors "are involved in informing very old parts of the brain about how much light is out there," Berson said, "affecting things like sleep and wakefulness, body temperature and hormone levels, and synchronizing the rhythms of those physiological variables with the rhythms of daylight and darkness."

The same nerve cells may also function as part of the pupillary system of the eye, widening or narrowing the center of the iris to let in more or less light as ambient light levels dictate.