Rods and cones hog all the credit for allowing us to see. But these light-sensitive neurons get some help from a much rarer kind of cell, according to a new study. If these unheralded cells are as important as the authors suspect, studying them may open the door to new therapies for some forms of blindness.
Scientists have known of the existence of these nerve cells, called melanopsin-containing retinal ganglion cells (mRGCs), since 2000. Research over the past decade has shown that they play an important role in reflexive responses to light, such as pupil constriction and regulation of the body's sleep-wake cycle. But they did not appear to be involved in vision.
In July, however, researchers reported in the journal Neuron that the stringy extensions, or axons, of mRGCs extend into parts of the mouse brain involved in conscious vision, not just the parts of the brain that control unconscious responses to light. The latest study confirms that finding and suggests that mRGCs enable mice to sense the brightness of their surroundings.
In the new work, researchers tagged the mRGCs with a blue protein to see where the cells occur in the mouse eye. When they tracked the cells' axons from the eye into the brain, they saw that many of them terminated in the lateral geniculate nucleus (LGN), the first relay station in the brain for visual information.
If mRGCs are involved in mouse vision, the researchers posited that light would produce activity in the visual centers of the brain in mice that lack rods and cones. To test this, they inserted thin wire electrodes into the LGNs of 18 mice and recorded electrical signals. "What we did is keep the mice in total darkness," says Timothy Brown, a neuroscientist at the University of Manchester in the United Kingdom. "And then we would switch on a light of a particular brightness for 60 seconds." The team tested a range of light intensities, from starlight to bright daylight, and found that light as intense as daylight fired up the LGN.
Brown and colleagues also looked at whether mRGCs might also send information to the LGN in mice with normal vision. "We found that approximately 40% of the brain cells that process visual signals appear to receive information from mRGCs," says Brown, whose team reports its work today in PLoS Biology.
"This is a particularly surprising finding since mRGCs themselves make up only 2% of the retinal cells that communicate to the brain."
What the researchers don't yet know is whether mRGCs can sense variations in brightness across the visual field that might allow them to distinguish between a dark wall and a brightly lit doorway, for example. If it's the latter, Brown says, the findings may open the door to new therapies for retinal degeneration. He envisions some sort of visual aid "designed to maximize the activity of these cells but notes that even if such therapies are possible, they won't be available anytime soon.
This is not the first paper to suggest that melanopsin cells play a role in conscious vision, says David Berson, a neuroscientist at Brown University and co-author of the Neuron paper, but it is "a significant new addition to a breaking story." However, he questions how relevant this line of research will be for blind people. The number of individuals with nonfunctional rods and cones that still have the ability to sense light is likely "vanishingly small," he says.
Samer Hattar, a neuroscientist at Johns Hopkins University in Baltimore, Maryland, and lead author on the Neuron paper, says he isn't convinced that the study proves that mRGCs are a key component of conscious vision in mice with functional rods and cones. Hattar points out that no group has yet shown that mice lacking melanopsin have inferior vision based on their behavior. "Just because you see something doesn't mean that it's going to be physiologically relevant," he says. "The story is not finished."