After taking a neuroscience or biology course, most students have heard about rods and cones. But what about the recently discovered third class of photoreceptor cells in the retina - intrinsically photosensitive retinal ganglion cells? While many scientists previously believed these mysterious cells were inherently different from other photoreceptor cells, recent findings show that ipRGCs adapt to light in a manner unexpectedly similar to that of rods and cones.
Prior to 2002, the scientific community had only known about two types of photoreceptor cells in the retina - rods and cones - that specialize in converting light energy into electrical signals that can be understood by the nervous system. Scientists, however, had suspected the existence of a third class of photoreceptor cells after observing how blind mice that lack rods or cones could still adjust their daily activities to daylight and night.
In 2002, Professor of Medical Science David Berson discovered ipRGCs, a special subpopulation of the ganglion cells at the last layer of nerve cells in the retinal complex. As a subgroup of ganglion cells - output cells that send signals to the brain - ipRGCs are able to communicate directly with the brain, while rods and cones have to communicate with other retinal cells and ganglion cells in order to reach the brain.
Kwoon Wong, a postdoctoral research fellow in neuroscience, joined Berson's lab in December of 2003 and is the lead author of the "Neuron" paper addressing ipRGCs' ability to adapt. Wong and Berson first identified the ipRGCs by using axon transport labeling, placing tracer dye in the circadian pacemaker of the brain of a rat so that the dye traveled onto those cells associated with the circadian pacemaker. They then exposed the rat ipRGCs to different light stimuli and recorded the electrical responses of the cells. Wong and Berson found the light stimuli evoked greater responses when the cells had been in darkness than when they had been exposed to bright background light, indicating that the cells did indeed adapt to different brightness levels.
According to Berson, ipRGCs are not involved in basic sight, but rather are involved in certain kinds of visual reflexes. Most notably, they take part in coordinating circadian systems with light.
The circadian system acts as a biological clock, monitoring the body's temperature, heart rate and other processes over a period of a day. It is driven by a "master pacemaker" inside the brain that keeps track of time as the body's functions fluctuate during the circadian rhythm's 24-hour cycle. Even if someone was placed inside of a cave, with no contact with the outer world, the body's functions would still continue to oscillate over a period of about 24 hours, Berson said. He added, however, that the inner clock is not perfect.
"It's like a cheap wristwatch that runs a little bit too fast or too slow," Berson said of circadian rhythms. "Every few days you have to check it and adjust the time back to what it's supposed to be." Human bodies can adjust their inner clocks to their environment, timing them to the sunrise each day. IpRGCs play a key role in this part of circadian rhythms, as they absorb light to maintain the synchrony between the environment and internal clocks.
While rods and cones function in basic sight to help someone catch a baseball or drive, ipRGCs are meant to deal with very gradual changes in light. Thus, they are considerably slower than rods and cones in their responses.
Along these lines, it seemed that ipRGCs would also differ from rods and cones in terms of their ability to adapt - that is, their ability to adjust their sensitivity according to recent stimuli. According to Berson, many people speculated that unlike rods and cones, ipRGCs might not adapt based on recent light exposure.
"Rods and cones adapt with a vengeance," Berson said. "But if the purpose of ipRGCs is to define when the sun has risen, they wouldn't want to adapt so much that they might be sensitive to, say, the stars or the moon rising." Considering the purpose of the cells, it would make sense for ipRGCs to be sensitive to an absolute light intensity, with their sensitivity pegged at a specific point, Berson said. Contrary to expectations, however, in vitro studies of ipRGCs have shown that the cells do adjust their sensitivities and adapt to different light intensities.
Wong and Berson are now focusing their research on learning more about the purposes of ipRGCs as well as studying exactly how the cells function on a chemical level. Wong is currently working on another article about how ipRGCs relate to other retinal cells in the synaptic network.
"We're making good strides," Berson said.
