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Eye Cells That Don't See, but Regulate

Posted on: Sunday, 16 April 2006, 06:00 CDT

By Tom Avril, The Philadelphia Inquirer

Apr. 16--As any good high school biology student can tell you, the human eye sees light with special cells called rods and cones.

But when George C. Brainard experimented with shining various colors of light into people's eyes, something odd happened:

A specific shade of blue light was most effective at shutting down the body's production of melatonin -- the "hormone of darkness" that helps regulate sleep and the body's internal clock. Yet that shade of blue is not one of the colors best detected by rods and cones.

His conclusion, shared by others conducting studies on blind people and animals: There must be some unknown cells in the eye -- some that responded to light but had nothing to do with seeing.

Since that experiment at Thomas Jefferson University, reported in 2001, other scientists have indeed found the new cells, as well as the gene that controls them. Only in the last year has a consensus emerged about how the new cells work.

The finding is just one of many in the exploding field of light therapy and its impact on the body's circadian clock -- and is getting attention in such diverse fields as architecture, psychiatry and space travel. Light is now touted as a way to alleviate depression, prevent jet lag, and boost alertness for those with unusual schedules, from astronauts to night-shift workers.

A few hospitals use different shades of light to keep nurses alert or keep patients restful. And some architects say the biological impact of light could one day change the very design of buildings.

An office with a window isn't just a status symbol, Brainard said. It actually could be good for your health.

After all, humans evolved in an outdoor environment, not beneath the fluorescent bulbs of the modern work space.

"Our whole relationship to architecture is going to shift," he said.

Yet there is cause for caution. Too much light can damage the eyes and skin. And too much at night, over a long period of time, may cause cancer by altering hormonal cycles.

Numerous therapeutic "light boxes" (boxes with various shades of light) have appeared on the market, unregulated by the FDA. The boxes' effects often are not backed by thorough research, said light-therapy expert Michael Terman.

"The claims are often outrageous," said Terman, of the New York State Psychiatric Institute at Columbia University Medical Center. "You can make things worse with light therapy if you don't do it right."

The field is barely two decades old, and many insurers don't cover treatment. Yet light therapy is clearly on its way to mainstream acceptance.

Last year, a team formed by the American Psychiatric Association reviewed all known research on the subject. Their conclusion: Bright light can ease both wintertime depression and the nonseasonal variety.

The positive effects, the team found, were equivalent to those found in most trials of traditional antidepressant medication.

Proper doses of light, in other words, may be just as good as a bottle of pills.

Shedding light in the dark

In a Jefferson University lab at 1:30 a.m., the curtains are drawn and the lights are low.

For Brett Coonradt, things are even darker. He has been blindfolded for several hours. But that is about to change.

A few minutes later, a technician draws blood from his arm. The blindfold comes off, and Coonradt is directed to stare into "the cannon," a metal sphere suffused with a piercing blue light.

"Awww," the research subject groans, blinking and rubbing his eyes. "Yeah, that's bright."

He will gaze at the light for 90 minutes, causing his pineal gland, a bean-sized cluster of cells near the center of the brain, to sharply curtail its production of melatonin.

The reason? The gland is getting a signal from a newfound messenger in the eye: photoreceptive ganglion cells.

The eye has many thousands of ganglion cells, most of which cannot detect light but instead help relay signals to the brain.

But a few hundred of the cells contain a light-sensitive protein called melanopsin, first discovered in African frogs, then in mammals and even in the lowliest one-celled organisms.

That protein helps convert light into an electrochemical signal that is then sent, indirectly, to the pineal gland.

And information about light exposure is going to many other parts of the brain, as well. Scientists still do not know the impact of all these messages, said Brown University scientist David Berson, who helped discover the light-detecting cells in 2002.

"A lot of it is still mysterious," he said.

A key recipient of these nonvisual messages is the hypothalamus -- the location of twin clumps of cells called the suprachiasmatic nuclei.

Together, they are known as the body's master clock.

Setting the clock

Our metabolism, body temperature, heart rate, hormone levels, and other bodily systems wax and wane every day.

The kidneys, for example, slow down at night. Otherwise, we'd have to go to the bathroom every two or three hours, said Jefferson's Brainard.

This cycle gets its cue from the master clock. It lasts close to -- but not exactly -- 24 hours.

Without light to keep them on track, our clocks would quickly veer off course -- a phenomenon reported in the 1970s.

Scientists still do not fully understand how light and the clock govern bodily functions. But research in the last decade is providing some big clues.

Melatonin, made by the pineal gland except when the ganglion cells detect light, seems to play a role in regulating sleep. It also has been shown to work as a mild sleeping aid when taken as a supplement. U.S. consumers bought $67 million of the hormone in 2004, according to Nutrition Business Journal.

Besides the ganglion cells, the eye's rods and cones also seem to help regulate the body's rhythms.

Researchers think light has potential for addressing numerous clock-related ills.

The use of light as medicine was proposed in the 1980s, when researchers first identified "seasonal affective disorder," or wintertime depression.

By supplementing short winter days with doses of artificial light, physicians could alleviate the seasonal blahs.

Today, light also is touted as a possible cure for eating disorders, irregular menstrual cycles, sleep problems, and the agitation suffered by some Alzheimer's patients.

While Brainard studies blue light, Columbia's Terman favors therapy with white light, prescribing machines that simulate the gradual approach of dawn.

Architects and engineers also are taking a new look at light.

It's a turnabout for professions that spent the last quarter-century saving energy. That meant fewer windows in some structures and only as much artificial light as needed to see.

"Now we're saying we've got to go in the other direction and raise the levels again," said Craig Bernecker, a consultant who taught architectural lighting design for 20 years at Pennsylvania State University.

That goal can be accomplished without compromising energy efficiency, he said, citing today's improved windows.

Yet researchers are years away from learning to design buildings with healthy light, said Bernecker, past president of the Illuminating Engineering Society of North America.

At least one application has emerged so far. Some hospitals use warmer, reddish light in patient rooms for its calming effect, while installing bluer, alertness-enhancing lights at nursing stations, Bernecker said.

Meanwhile, the studies continue at Jefferson, with various experiments held two or three nights a week.

Though Brainard oversees the work, he doesn't do the nighttime routine anymore. When he was in his 40s, a lab manager told him he was sluggish for two or three days after pulling a night shift.

Also, for the first time in his life, he began to experience jet lag after long trips.

"My biological clock aged, and I hit the wall," said Brainard, who is now 55.

But though his clock has aged, he is still committed to finding out what makes it tick.

Contact staff writer Tom Avril at 215-854-2430 or tavril@phillynews.com.

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Source: The Philadelphia Inquirer

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