April 28, 2008

How Eyes See More Than Images

Rod and cone cells. A section of retina shows the thinner rods and wider cones.Chris Guerin, Wellcome Images.

New research shows that a particular kind of cell in the eye is crucial for light-related functions other than seeing. Mice without the cells can still see, but their pupils don’t constrict or dilate normally, and their circadian rhythms don’t change with the light cycles in their environment. A better understanding of these separate modes of light detection may eventually help people with sleep problems or seasonal depression.

Cells in the eye called rods and cones are the ones 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 our brains 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.

About 2% of RGCs—called intrinsically photosensitive RGCs, or ipRGCs—make a protein called melanopsin that allows them to sense light on their own and send information about light intensity to the brain. Previous research has shown that mice genetically engineered to lack melanopsin have reduced non-image-forming functions like pupil constriction. But because the mice don’t completely lose these functions, rods and cones must also be sending non-image-forming signals to the brain. A research team led by Dr. Samer Hattar at Johns Hopkins University set out to discover which RGCs are responsible for relaying these signals from the rods and cones. Their work was supported by NIH’s National Institute of General Medical Sciences (NIGMS), National Eye Institute (NEI) and other sources.

The scientists reported in the online edition of Nature on April 23, 2008, that they inserted a toxic protein into the gene that normally encodes for melanopsin, killing the cells and creating mice without ipRGCs. Several different tests showed that the mice without ipRGCs had normal vision in most respects. However, they had a severely reduced ability to constrict their pupils when exposed to a range of light intensities.

The researchers next assessed the wheel-running activity of the mice during different light/dark cycles. They found that the mice without ipRGCs didn’t synchronize their activity in response to different light cycles like normal mice did. In both these non-image-forming functions, mice that completely lacked ipRGCs had more extensive defects than mice engineered simply not to make melanopsin.

"This research illustrates that there are 2 distinct pathways for the 2 different aspects of light detection: image-forming and non-image-forming," Hattar said. Image-forming light detected by rods and cones travels through RGCs to the brain. Light information that’s not used to form images is sent to the brain predominantly through ipRGCs. These cells work both by sensing light information themselves and by relaying signals from rods and cones.

—by Harrison Wein, Ph.D

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