Photopigment's Role in Vision Illuminated

Melanopsin is perhaps most widely known as the light sensor that sets the body's biological clock, but now it is also reported to play an important role in vision. Via messengers called melanopsin-expressing retinal ganglion cells, or mRGCs, it forwards information about the brightness of incoming light directly to conventional visual centers in the brain, according to an international collaboration of scientists in a recent issue of PLoS Biology.

Melanopsin-expressing retinal ganglion cells extend their axons – long, slender projections that connect with other neurons – all the way to the primary processing center for visual information received from the brain. (Photos courtesy of Satchidananda Panda, Salk Institute for Biological Studies, and James Fitzpatrick, Waitt Advanced Biophotonics Center.)

The findings reveal a new role for mRGCs during image-forming vision and suggest that these cells could make a significant contribution to assessing the intensity of light and supporting vision even in people with advanced retinal degeneration, the researchers said.

"Millions of people worldwide suffer varying degrees of blindness because of rod and cone degeneration or dysfunction, but many of them can still perceive differences in brightness," said senior author Satchidananda Panda, an assistant professor in the Regulatory Biology Laboratory at the Salk Institute for Biological Studies. "Melanopsin-expressing RGCs typically survive even complete rod and cone loss and could explain the light responses under these conditions," he said.

For the greater part of 100 years, it was thought that the ability to convert light into electrical signals in the mammalian retina was restricted to only two types of photoreceptors: rods and cones. This view changed dramatically when Panda discovered the existence of a third type of mammalian photoreceptor, which is only present in a few thousand cells embedded in the deeper layers of the retina.

Melanopsin, a light receptor that measures the intensity of incoming light is found in rare, specialized cells embedded in the retina. The different colors corresponds to different depths of the imaged tissue sample.

Melanopsin, a photopigment that measures the intensity of incoming light, is fundamentally different from the classical rod and cone opsins, which help us see. For one, it is much less sensitive to light and has far less spatial resolution-characteristics that fit perfectly with this light sensor's primary function of signaling changes in ambient light levels to the brain throughout the day.

It sends its signals directly to the human circadian clock, which sits just above the point where the optic nerves cross. Although only half the size of a pencil eraser, it synchronizes the body's daily rhythms with the rising and setting of the sun, telling the body when it is time to go to sleep, when to be hungry and when to wake up. But it does more than that. Just like a meter in a camera that allows the aperture to be adjusted, mRGCs also control pupil size.

Until now, however, it was unknown whether mRGCs also contribute to conventional image-forming vision, especially the as-yet poorly understood mechanism of "brightness" and "lightness" perception.

To find out, Panda and his collaborators at the University of Manchester in the U.K. traced individual mRGCs' axons –long, slender projections that connect with other neurons – from the retina through the circadian clock and onward. They discovered that the axons reached all the way to the lateral geniculate nucleus (LGN), the primary processing center for visual information received from the retina.

"We found widespread light responses in the LGN and visual cortex, even in mice lacking functional rods and cones, which are often used as a model of advanced retinal degeneration," Panda said. He hopes that it might be possible some day to impart vision to blind individuals by gene therapy with a re-engineered melanopsin.

"The density of mRGCs in the retina is too low for any meaningful resolution," he said. "But if we could express melanopsin in a greater number of cells, we might be able to increase resolution to a point that allows blind people to safely navigate their environment."

Researchers who also contributed to the work include Timothy M. Brown, John Gigg and Robert J. Lucas at the University of Manchester, in the U.K.; Carlos Gias, Ma'ayan Semo and Peter J. Coffey at University College London; and Megumi Hatori and Sheena R. Keding at the Salk Institute. The work was funded by grants from the Wellcome Trust, the National Institutes of Health, the Dana Foundation, a Pew Scholar award and the London Project to Cure Blindness.

For more information, visit: www.salk.edu