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New light-sensitive pathway in the eye offers drug target to control sleep

17 August 2008 

A set of nerve cells in the eye control our levels of sleepiness according to the brightness of our surroundings, Oxford University researchers have discovered. The cells directly regulate the activity of sleep centres in the brain, providing a new target for the development of drugs to control sleep and alertness.

Immune systems, cognitive performance, and mental health are all affected by the body’s sleep-wake cycle. Sleep disruption is known to be associated with a range of problems, including depression, immune impairment and a greater risk of cancer. Many drugs have been developed to modify sleep-wake cycles but these are crude, affecting many chemical pathways and different parts of the brain at the same time, and have side-effects.

“Sleep and the disruption of sleep patterns is a huge problem in the 21st century,” says Professor Russell G. Foster of Oxford’s Nuffield Laboratory of Ophthalmology, who led the work. “Our working culture of long hours and shift work, with the 24/7 availability of almost everything, have conspired to demote sleep in our priorities.”

The presence and absence of light can affect levels of sleepiness and alertness. It’s why dimly lit rooms lead us to feel drowsy, while bright lights stimulate wakefulness. During the Second World War it was shown that brightly lit factories had a more alert and productive workforce than dimly lit factories, but until now little was known about how this happened.

“We have discovered a new pathway that modulates sleep and arousal,” Professor Foster explains. “If we can mimic the effect of light pharmacologically, we could turn sleep on and off."

Professor Foster and colleagues have previously shown that the eye contains a subset of retinal nerve cells that are sensitive to light. Working on mouse models in which these retinal ganglion cells have been turned off genetically, the research team found that the effects of light on sleep and alertness were completely abolished. The work was supported by the Wellcome Trust and a European Commission grant.

Mice are nocturnal animals, so show the opposite light response to humans. They are alert and active in the dark, but go to sleep in the light. The Oxford team videoed mice and monitored their muscle and brain activity for four hours in the dark. The lights were then switched on for an hour and after 15–20 minutes the mice went to sleep. Turning off the light-sensitive retinal ganglion cells abolished this behaviour. The mice stayed awake when the lights were on.

“There was absolutely no effect on the mice. This was a very clear and very surprising result,” comments Professor Foster.

The researchers were able to track this sleep pathway to the brain. They showed that two sleep-inducing centres in the brain are directly activated by the cells, turning on or turning off sleep. By defining the whole light-responsive system that regulates sleep and alertness, the researchers have found a new pathway that could provide a new therapeutic target for manipulation of sleep and arousal in humans.

Two video files to accompany this news release are available from the Press Office, University of Oxford, 01865 280530, press.office@admin.ox.ac.uk. These .avi files of 24 seconds and 14 seconds show a normal mouse going to sleep under the lights and a mouse that has had its light-sensitive retinal nerve cells turned off genetically staying awake.

For more information please contact Professor Russell Foster at russell.foster@eye.ox.ac.uk

Or the Press Office, University of Oxford, 01865 280530, press.office@admin.ox.ac.uk.

Notes to Editors

  • ‘The acute light-induction of sleep is mediated by OPN4-based photoreception’ by Daniela Lupi, Henrik Oster, Stewart Thompson and Russell G. Foster, is to be published in Nature Neuroscience. It is embargoed until 18:00 BST / 13:00 US Eastern time on 17 August 2008.
  • How the eye enables us to see is well known: light is detected by the rod and cone cells of the retina, their electrical signals are assembled into an image by groups of retinal nerve cells, and the images further processed in the brain. This picture was enlarged 15 years ago when Professor Russell Foster’s group identified a third type of cell in the eye that is sensitive to light. The research team have shown that a small group of retinal ganglion cells detect light and shift our body clocks to new time zones and allow recovery from jet-lag. This paper in Nature Neuroscience now reports the discovery of a new role for light detection in the eye beyond vision and the setting of our body clocks: the direct regulation of sleep according to light levels.
  • Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University’s income and expenditure, and two-thirds of its external research income. Oxford’s world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.
  • The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk

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