17:45 11 June 2008
NewScientist.com news service
You might call it our circadian eye. A handful of retina cells sense light, not for vision, but instead to reset our body clocks each day. Killing off these cells in mice leaves their sight unharmed, but throws their clocks out of whack, two new studies show.
Jolting these cells back into action might offer salvation to insomniacs, whose circadian cycles are slightly off, says Satchidananda Panda, a molecular biologist at the Salk Institute in San Diego, who led one study. Natural degeneration of these cells could also explain why insomnia often strikes the elderly.
“Maybe we can develop an eye drug to reset your clock,” he says.
Alternatively, triggering the cells with extra-pale blue light – the wavelengths they’re most sensitive to – could do the same trick, says Samer Hattar, a neuroscientist at Johns Hopkins University in Baltimore. Hattar’s team identified the same role for the cells, which produce a recently-discovered light sensor called melanopsin.
Clocks going back
The first evidence for our circadian eye came in the 1920s, when an American physician noticed that congenitally blind mice can still dilate their pupils – a sign of light detection – despite lacking rods and cones, the photosensors that transform light to vision.
Little came of this observation until the 1990s, when scientists chanced on a new light sensor in frog skin and later found a close cousin in humans and mice. The cells that make melanopsin forge a link to the brain region that winds the circadian clock.
But when Panda’s team knocked out the gene from mice, the rodents’ clocks still sensed light, perhaps because other cells filled in the gap, he says.
To remove this crutch, Panda and Hattar independently engineered mice that lost these cells well after birth. Hattar’s team spliced in a gene that makes a killer toxin produced by diphtheria, while Panda’s group injected the same toxin to cells engineered to sop up the poison.
The results were nearly identical. Mice with destroyed cells could still sense light with their retina, and the rodents steered clear of an illusory cliff that blind mice trammel across.
But the mice couldn’t reset their circadian clocks. Without a daily light cycle, mice keep a 23.5-hour day. This is exactly how the mutant mice behaved when researchers logged the rodents’ daily spins on a running wheel.
Normal mice exercise at the same hour, day after day. But even when exposed to 12 hours of light followed by 12 hours of dark, the mice without melanopsin cells worked out a half hour earlier with each day.
“When there’s no photoreceptor, the mice have the normal circadian clock but they can’t entrain their clock to light and dark,” Panda says.
So far no one has shown that a broken “circadian eye” causes sleeping problems in humans, but Hattar suspects it’s a matter of time. Slight genetic differences in the human melanopsin gene could affect our circadian clocks, with some versions working better than others.
“I’m sure somebody’s looking at that and I’m sure that somebody will find some melanopsin defects,” he says.
And because the cells also control pupil dilation, people with damaged ones should be easy to spot, says Russell Van Gelder, an ophthalmologist at the University of Washington in Seattle. He figures about 1 in 10,000 people has this problem.
“If you ever see anyone whose pupils are coming wide open when they’re watching a baseball game, send them to me, I want to see them,” he says.
Journal reference (Panda et al): PLoS ONE, DOI: 10.1371/journal.pone.0002451
Journal reference (Hattar et al): Nature, DOI: 10.1038/nature06829
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