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Eye Cells May Help Regulate Body's Clock

Editor's Note: (Reprinted from The New York Times, February 8, 2002) Editor's Note: This article is reprinted from the Braille Forum, Volume XL, No. 11, May 2002.

With the help of three kinds of blind mice and some ugly frogs, scientists have discovered a new class of light-sensing cells in the retina. The cells, which are different from the rods and cones that enable vision, appear to reset the body's master biological clock each morning and night. The researchers said that while the finding was made in mice, it was certain to hold true for humans, with implications for possible treatment of sleep disorders, jet lag, depression and other maladies involving the body's internal clock.

"We thought we knew everything about the retina," said Dr. Michael Menaker, a neuroscientist at the University of Virginia and an expert on biological clocks, who is familiar with the research. "Now we find we have two separate systems in the eye, one for vision and one for setting the clock. We have a new way of thinking about how light is interpreted by the nervous system."

Dr. Ignacio Provencio, an assistant professor of neuroscience at the Uniformed Services University in Bethesda, Md., whose work on frogs helped lead to the discovery, called it "heretical." Not every day, Dr. Provencio said, do scientists find a new body function.

The cells were discovered by Dr. David Berson, an associate professor of neuroscience at Brown University, and are described in today's issue of the journal Science.

Dr. Berson said a deeper understanding of the new photoreceptors might lead to novel treatments for disturbances of the body's internal clock. It may turn out that people who have defects in the newly described system could suffer from "time blindness," similar to colour blindness.

The traditional view of how light is handled in the eye has held for more than 100 years, Dr. Berson said. It states that the retina has only two kinds of light-sensitive cells: rods and cones. Together they carry out two jobs. One is to capture light and send it to the brain, where images are formed in visual processing. The second is to send light-induced signals to a tiny region in the brain that sets the body's biological clock.

This region, called the suprachiasmatic nucleus or SCN, is just above the optic nerve on both sides of the brain. A pinhead speck of tissue, the SCN measures the passage of every 24 hours by making and consuming proteins in precisely timed fashion --letting the body know when to wake up and when to go to sleep. This circadian clock works independently to measure time, Dr. Berson said, though it must be resynchronized every day as light levels change with the Earth's movement around the sun. But experiments over the last five years --Dr. Berson calls them "head scratchers" --raised questions about the role that rods and cones had long been assumed to play in setting the biological clock.

Three kinds of blind mice posed the problem, said Dr. Russell Foster, a neuroscientist at Imperial College in London. The first was a mutant mouse that lacked all its rods and 95 percent of its cones. "These animals are blind, yet they are as good at responding to light in setting their daily rhythms as their sighted litter mates," Dr. Foster said. Perhaps the biological clock could be reset with just a few cones.

To find out, Dr. Foster and his colleagues genetically engineered a coneless, rodless mouse. These completely blind animals aligned their clocks to natural light and dark cycles just as normal mice did. In a third experiment, Dr. Foster removed the eyes from mice. They could no longer set their biological clocks in response to light.

Meanwhile, Dr. Charles Czeisler, a physician at Harvard Medical School, found similar patterns in blind people. Some, without rods and cones, could set their biological clocks in response to daily changes in light levels. Others could not.

Then Dr. Provencio found a head scratcher --a light- sensitive molecule in the skin cells of the African clawed frog that changes colour when the light changes. The molecule, melanopsin, is in the family of proteins that help convert photons of light into electrical and chemical signals used by the nervous system. Rods and cones use rhodopsin, a mammalian protein in the same family. A search in genetic databases turned up a surprise. Melanopsin is found in a small number of ganglion cells in the retinas of mice, monkeys and humans. Moreover, these ganglion cells project to the SCN, the region that sets the body's clock.

"When I heard this, my eyes got huge," Dr. Berson said. To find out whether the ganglion cells reacted to light, he isolated them so they had no contact with rods or cones and monitored their electrical activity. "I'll never forget the first time we did the experiment," Dr. Berson said. "We gathered around the rig. The cell was sitting in darkness. We hit it with light. Nothing happened for almost a second. Then all of a sudden it began to spike. We went crazy. The missing photoreceptors in the retina and the cells that talk to the clock are one and the same."

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