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Eye Cells Are Out of Sight

A new study sheds light on how a particular kind of cell in the eye—crucial for light-related functions other than seeing—detects light and communicates with the brain. A better understanding of these cells may eventually help in the development of treatments for sleep problems or seasonal depression.

Cells in the eye called rods and cones are primarily responsible for detecting light. They send signals to the brain through retinal ganglion cells (RGCs) so the brain can form our perception of images.

But our eyes do more than help create images of our surroundings. Our pupils respond to light intensity—constricting in bright light to reduce the amount of light entering the eye and dilating when it’s darker to let more light in. Our bodies’ circadian rhythms—when we’re active and when we sleep—are influenced by the light/dark cycles of both the sun and the artificial lights we use.

Studies have found that the brain signals governing these non-sight functions of the eye don’t all come from rods and cones. In recent years, researchers have pinpointed a small subset of RGCs—called intrinsically photosensitive RGCs (ipRGCs)—that are crucial for maintaining circadian rhythms and for pupil constriction and dilation, among other functions. The cells make a protein called melanopsin that allows them to sense light on their own and send information about light intensity to the brain.

A research team led by Dr. King-Wai Yau at Johns Hopkins University School of Medicine set out to learn how ipRGCs respond to light to drive behavior. Their work, which was supported by NIH’s National Eye Institute (NEI) and others, appeared online in Nature on December 31, 2008.

The team first tested the light sensitivity of ipRGCs by flashing light and recording the electrical current generated by single cells. They found that ipRGCs are not very sensitive to light. In fact, they’re less sensitive than cones, which are responsible for vision in bright light.

The researchers next used a flash so dim that only a single melanopsin molecule in each cell could be activated by a photon. They found that each activated melanopsin molecule triggered the cell to transmit a signal all the way to the brain. However, they calculated that the density of melanopsin in ipRGC membranes is nearly 10,000-fold lower than that of rod and cone pigments.

The researchers next examined pupil constriction in mice that had been genetically altered to be free of rod and cone function. Flashing light at mice sitting in the dark, the scientists found that, on average, a few hundred light-activated melanopsin molecules are enough to trigger a pupil response. Nonetheless, it takes a good deal of light to reach that threshold, the researchers say.

These results show that ipRGCs capture very little light but, once captured, the light is very effective in producing a signal to the brain. “In terms of controlling the pupils and the body clock, it makes sense to have a sensor that responds slowly and only to large light changes,” Yau says. “You wouldn't want your body to think every cloud passing through the sky is nightfall.”

Among the researchers’ future aims, one is to discover how ipRGC signals are processed in the brain. Eventually, they hope to unravel what goes wrong in disorders like seasonal affective disorder and jetlag.

—by Harrison Wein, Ph.D.