Good timing. Blue-stained melanopsin-containing retinal neurons connect with the brain's clock (dark blue).

Breakthroughs 2002: Retina Receptors

Researchers hit the jackpot this year in understanding how light resets the circadian clock, our internal timepiece that regulates daily patterns of behavior and physiology. After years of searching hard for the so-called photoreceptor cells that relay that light signal to the clock in mammals, circadian biologists had tantalizing clues but no answer. They knew the photoreceptors must be in the eye. But the eyes' only known photosensitive cells, the rods and cones, weren't doing the job. Then last winter, five independent research teams discovered a brand-new class of light-responsive cells in the mammalian retina that connect directly to the brain's clock.

First, researchers found a pigment called melanopsin in a small subset of retinal ganglion cells (RGCs) in the eyes of rats. Most RGCs don't respond to light, but it turned out that the melanopsin-containing ones do, making them a brand-new class of previously unknown light-responsive retinal cells. What's more, researchers traced their connections and found that they hook up directly to the suprachiasmatic nucleus, the brain area that houses the clock.

That's not all. More recent neuroanatomy studies have shown that the melanopsin-containing RGCs also link up to brain areas that control a variety of responses to light that don't require the image-forming visual system, such as constriction of the pupils and the direct effect of light on sleep-wake state--what makes us drowsy in dark seminar rooms or wakeful if the lights are kept on all night.

Most of the pieces have fallen neatly into place, but technical difficulties prevented researchers from proving that melanopsin responds chemically to light. Without that evidence, some were reluctant to accept it as the RGCs' light-capturing pigment. Now that issue has been put to rest: In last week's issue of Science (13 December, pp. 2211 and 2213), researchers showed that mice that lack melanopsin do not normally reset their circadian clocks in response to light, suggesting that melanopsin is capturing and relaying the light signal.