- Cone photoreceptors in retinal degeneration have been thought to be dormant
- However, new research suggests cone photoreceptors in a degenerating retina may continue producing responses to light.
- Researchers recorded downstream signals from the retina that indicate visual processing was not as compromised as might be expected.
In the retina, the cells responsible for the visual experience are rods and cones.
These cells are called photoreceptors and they absorb and convert light into electric signals.
Rods are active in dim light. Cones are active in daylight and help a person see colors.
Alapakkam Sampath, the chair of ophthalmology at the the University of California Los Angeles’ Jules Stein Eye Institute and a professor at the David Geffen School of Medicine at UCLA, has spent the past quarter of a century studying how photoreceptors in the retina work.
“The photoreceptor cell is the the only conduit for our visual experience,” Sampath told Medical News Today. “When photoreceptors begin to die, it results in blindness, which is quite debilitating for us as humans given that so much of our brain is dedicated to processing visual images.”
Sampath was the senior author of a study published in the journal Current Biology that suggests that cone photoreceptors in the degenerating retina of mice continue to function and are able to produce responses to light.
Understanding the nature of dysfunction
Retinitis pigmentosa is a group of inherited diseases that cause the photoreceptors to die, folic acid and iodine in pregnancy resulting in vision loss and eventual blindness. The condition
Initially, retinitis pigmentosa affects the rods, which causes night vision issues. As the rods die off, the ailment begins to affect the cones, leading to blindness.
“Typically in the literature they’ve always been called dormant cones,” Sampath explained. “The dormancy has embedded in it the notion that they’re not doing anything.”
Sampath and the other researchers set out to understand the “nature of the dysfunction.”
“Because I think this is the way to figure out whether [the photoreceptors] can be repaired or to what extent they could be rescued,” he said.
To do this, the researchers “studied the photoreceptors that are left when other photoreceptors are degenerating,” Sampath said.
Specifically, they made patch clamp recordings from cells in the central region of the retina in
The patch clamp method is a refined electrophysiological technique that measures the membrane potential as well as the amount of current passing across the cell membrane.
Additionally, researchers used
Less sensitive but active
The researchers said they were surprised to find many of the cones were able to respond to light.
“We showed that they were remarkably still active, although a lot less sensitive than normal,” Sampath said.
Researchers observed light response in four out of four cones in mice that were 3.5 weeks old as well as 7 of 10 cones in mice that were 6 weeks old and 1 out of 3 cones at 9 weeks old.
The sensitivity of the cones was about 100-fold to 1,000-fold less than normal.
The cells also displayed many of the features of normal cones. This included similar
Greg Field, an adjunct associate professor of neurobiology at the Duke School of Medicine in North Carolina, led a part of the study that looked at
“What Greg’s laboratory worked on is recording signals from all of the residual cones as they are represented in the ganglion cells,” Sampath explained. “What he found was surprisingly that the loss of sensitivity at the level of the ganglion cells was not as much as you might predict based on the loss of sensitivity we saw in the photoreceptors, so there must be some type of adaptation or compensatory mechanism that’s trying to protect signals… The brain and the retina as an extension of the brain tries super hard to ensure that function is protected for as long as possible at the highest quality possible.”
These cones might be key to figuring out how to repair lost sight.
“What Greg showed in his study is that the spatial properties of the cells as well as the time scale on which they’re active are not changed that much,” Sampath said. “It’s only that the sensitivity is reduced so the potential is there is if the sensitivity of the cones could be restored or increased… you might actually have nearly normal daytime vision. So these residual cones may be a great conduit for rescuing visual experience that must be debilitating. We don’t know how how much more visual loss there is. We haven’t done the behavioral tests on these mice under these conditions, but the presumption is that… their vision is far less sensitive.”
Dr. Howard Krauss, a surgical neuro-ophthalmologist and director of Pacific Neuroscience Institute’s Eye, Ear & Skull Base Center at Providence Saint John’s Health Center in California summed up the results of the research to Medical News Today this way:
“So the significant science of the article is that even after nerve cells, in this case retinal photoreceptors, have lost their ability to transmit a detectable signal by the organism, even after the [rodent] is blind, this study is demonstrating that there still is light responsiveness of the photoreceptor. And therefore, it speculates that there should be some way of amplifying that responsiveness or interrupting the degenerative process to potentially restore vision.”
More research needed
Krauss, who was not involved in the study, said he appreciates the use of rd10mice for research. “rather than experimenting on people who have retinitis pigmentosa. You can use this mouse model to experiment either by genetic manipulation or medical manipulation to see if you can amplify the retinal response.”
Reflecting on the study as a whole, Krauss said that “it’s not that surprising that a non-functional nerve cell would still have some responsiveness, even though there might not be any light perception.”
He stressed the research is at an early stage.
“It really is very speculative that this is going to lead to anything of therapeutic use,” he said. “And it certainly is too early in the in the research to write an article that would say, ‘Great news, retinitis pigmentosa will be cured.’”
Krauss also emphasized that the study is looking at vision loss caused by retinitis pigmentosa.
“So we can’t look at what he’s discovering in this article as a potential intervention for things like macular degeneration or diabetic retinopathy or other retinal degenerative diseases,” he said. “It really only applies to the degenerative process that occurs in conditions like retinitis pigmentosa.”
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