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Illuminating the biological clock

Copyright: Russell Foster group

As recently as 25 years ago, if you’d have suggested that human behaviours like sleep, mood, appetite and sex drive were heavily influenced by structures in our eyes you would have been laughed out of town.

For more than one hundred and fifty years it was thought that human vision had two cellular components: the rods and cones, for low light and colour vision respectively. But from the 1990s, this orthodoxy was spectacularly overturned by Professor Russell Foster of the University of Oxford. His group discovered a third class of receptor, photosensitive retinal ganglion cells (pRGCs), that detect daylight and regulate a wide range of physiologies by keeping our 24-hour body clocks in tune with the environment. Without daily re-setting by light, our biological day would soon drift out of alignment with the astronomical day.

Data breakout

2M Number of people in the UK who live with sight loss (~360,000 are registered as blind or partially sighted)
1991 Foster’s first paper showing mice with no rods or cones still show normal circadian responses to light
2012 Foster becomes director of the new Sleep and Circadian Neurosciences Institute (SCNi)

Funded by BBSRC responsive mode grants and the NEURON initiative, Russell’s work was classic biological detective work. Animals such as birds and amphibians sense daylight through their thin skulls; the human cranium is too thick for this, so he surmised that our eyes had contain light-detecting neurons for non-visual tasks such as regulation of rhythmic biology. Looking more closely at mammals than anyone else, he found them.

Facing severe initial resistance to the idea, he set about proving their role by engineering mice to have eyes without the rod and cone receptors. But they could still reset their internal biorhythms, unless their eyes were covered. “BBSRC had the courage to take my grant applications seriously and funded a huge chunk of the work that led to the discovery of a new class of photoreceptor, first in fish, then mice and ultimately in humans,” says Foster.

The research has had significant impacts in the clinic. “Ophthalmologists now appreciate that our eyes provide us with both our sense of vision and our sense of time, and this understanding has changed the clinical definition of blindness and the treatment of eye disease,” says Foster. For example, patients who have lost their rods and cones as a result of inherited gene defects, but retain normal pRGCs, should be encouraged to seek out sufficient day-time light to ensure the body clock is adjusted to environmental time. Furthermore, every effort should be made to preserve the eyes of visually blind individuals but with intact pRGCs, otherwise individuals will be condemned to a lifetime of poorly regulated sleep – rather like constant jet-lag.

Foster has since gone on to research a host of physiologies and pathologies related to absent or poor sleep, including the effects of different lighting in offices, and the wavelengths associated with mobiles phones and tablet. See his talk at TED Global 2013.