Descent of Man
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Researchers find new photoreceptor and visual system in the eye
Posted: Wednesday, February 6, 2002
Brown University

PROVIDENCE, R.I. — Brown University researchers have found a new cell in the eye that acts as a photoreceptor – like a rod or cone – and sets the body’s circadian clock.

For nearly 150 years, scientists considered rods and cones to be the eye’s only photoreceptors – cells that turn light energy into electrical impulses. Many cells in the eye and brain respond to light but only because they are linked to the rods and cones by complex pathways. These cells are responsible for the nervous system’s sensitivity to patterns, objects and movement in the visual world.

Now there is a third photoreceptor, say scientists at Brown. The new cell resides deeper in the retina than rods and cones and looks remarkably different, more like the underside of a canopy of twisted tree branches.

The scientists dub the new cell “an intrinsically photosensitive ganglion cell.” It also turns light energy directly into brain signals. These signals govern the body’s 24-hour clock, they say, adding that this retinal input is what helps people get over jet lag.

In the February 8 issue of Science, the researchers describe the new cells, discovered in the retinas of rats, and their direct pipeline to the brain. The cells send out nerve fibers which travel within the optic nerve and connect with the clock region in the brain.

“We think this population of cells plays a role in setting the circadian clock and probably in a variety of other functions where all the brain needs to know is how bright it is,” said lead author David Berson, associate professor of neuroscience. “It is a visual system that runs parallel to the one we have been thinking about all these years. Now we have to rethink how the retina works and how the brain understands what is going on in the visual world. This is a new kind of representation of light by the nervous system, a new way for the brain to react to the visual environment.”

The scientists went looking for the cells in an effort to explain why some people who are functionally blind – whose rods and cones do not work – can still adjust their biological rhythms to match the day and night of the external world.

“There is a strong likelihood that there are identical cells in humans,” Berson said. “This could explain why certain people who are functionally blind due to retinal degeneration continue to set their biological clock according to the day/night cycle. These people have suffered damage to photoreceptors and to a visual system we knew about. What we didn’t know until now was what sort of photoreceptor system still operated.”

In experiments, the researchers injected a fluorescent dye into the tiny part of a rat’s brain that governs the 24-hour clock cycle. The dye traveled back to the new photoreceptors in the eye. The researchers then found the dye-filled cells, recorded their electrical activity, and found that they continued responding to light whether or not they were connected to the retina or brain.

“We concluded that a response to light was intrinsic to these cells,” Berson said. Although scientists have long known that ganglion cells – the output cells of the retina – play a key role in vision, they were not considered to have any photoreceptors among them.

A photoreceptor is a cell in the eye that contains a chemical called a photopigment that changes its properties in response to light. This change triggers a cascade of biochemical reactions and an electrical response in the photoreceptor. This signal then moves along a pathway between the cells and the brain.

The paper’s coauthors include undergraduate Felice Dunn and postdoctoral researcher Motoharu Takao. The National Eye Institute funded the research.

Berson and Takao are two of the co-authors of another paper in the February 8 issue of Science that points to the chemical melanopsin as the likely photopigment in these cells and traces their pathways to the brain. The other authors of that paper are from the Howard Hughes Medical Institute and Johns Hopkins University School of Medicine.

The newly discovered retinal photoreceptor, right, is an intrinsically photosensitive ganglion cell. The transduction of light into electrical signals appears to take place throughout the cell body (the dark, dyed circular structure) as well as in its slender, tangled dentrites.

In this recording, the cell’s electrical activity has been transformed so the human ear can hear it. As the recording begins, the cell sits in the dark, awaiting a stimulus. About 10 seconds into the recording, a tone sounds, marking the moment when a bright light is turned on and kept on. For several seconds, there is no detectable response from the cell, but eventually it begins to fire nerve impulses, heard as popping sounds. The delay between the onset of stimulus and the beginning of the response is extraordinarily long compared with conventional photoreceptors (rods and cones). This is presumably because the newly discovered photoreceptors are specialized to detect slow changes in environmental lighting, not the rapid events that are so important in pattern vision. With constant light stimulation, the rate of firing gradually increases and then plateaus at a rate that encodes the intensity of the light flooding the cell.

[See also statement by sleep researcher Mary Carskadon.]

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