Wednesday December 10 2014
Researchers managed to create new light-sensitive cells
"Procedure to restore sight in dogs gives hope for future blindness cure," The Independent reports.
Researchers have restored some modest degree of light sensitivity (though not full vision) in animals who have a similar condition to retinitis pigmentosa.
Retinitis pigmentosa is an umbrella term for a group of human inherited eye conditions, affecting around 1 in 4,000 people, in which the normal light-sensing cells contained in the retina become damaged or die.
Experiments on blind mice and dogs have found cells in the retina that are not normally light-sensing (retinal ganglion cells) can be genetically modified to respond to light.
The researchers used gene therapy to modify these cells. The cells responded to light after they were activated with an injection of a chemical called MAG, with the effects lasting up to nine days.
In some of the experiments, blind mice treated in this way were able to see light again and move around like sighted mice in a maze.
The researchers also carried out similar experiments using blind dogs to see if the method would work in a large animal.
Laboratory experiments were able to show ganglion cells in dogs could also respond to light. However, there were no experiments that showed whether the dogs could see again.
No human trials have been performed yet, but the researchers hope this will not be too far off.
Where did the story come from?
The study was carried out by researchers from the University of California, the University of Pennsylvania, and the Lawrence Berkeley National Laboratory.
It was funded by the US National Institutes for Health, the National Eye Institute, and the Foundation Fighting Blindness.
The study was published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences of the United States of America.
The Independent and the Mail Online accurately reported the study, although the headline writers took the usual liberties. While both acknowledged the research involved dogs and mice, claims the animals had their sight "restored" is an overstatement.
The headlines also failed to point out this technique would only have a potential application in cases of retinitis pigmentosa and not more common causes of visual impairment, such as age-related macular degeneration.
What kind of research was this?
This animal study tested whether cells in the retina that do not respond to light could be made to respond. They used genetic modification to produce a light receptor protein and a light-sensing chemical compound. This two-step process was tested on the retinas of blind mice and dogs.
In the inherited human condition retinitis pigmentosa, there is a progressive loss of rod receptors (light-sensitive cells) and cone receptors (colour-sensitive cells). This causes tunnel vision and, eventually, blindness.
Previous research found that although there is loss of these photoreceptors on the outer level of the retina, the connecting nerves underneath still function.
Researchers were interested in whether they could get these connecting nerves (retinal ganglion cells) to act as light-sensing cells, which could restore some vision.
What did the research involve?
The researchers first used genetic engineering to insert a gene for a receptor that responds to light in the presence of a chemical called maleimide-azobenzene-glutamate (MAG).
This process uses a modified virus called adenovirus to carry the gene into cells. The genetically modified virus is injected into the retina. The scientists were able to get retinal ganglion cells to produce this receptor.
Afterwards, an injection of MAG could turn on the light receptors when they are exposed to light. However, the first set of laboratory experiments did not work well because the level of light required to activate the new light receptors was so high that it damaged the retina.
After modifications, they produced a slightly altered chemical compound called MAG460, which responded to a less damaging wavelength of light, and performed a set of experiments.
Mice genetically engineered to lose the function of rods and cones by the age of 90 days were used. The researchers injected the mice's retinas with the adenovirus containing the light receptor gene.
Afterwards, they injected the retinas with MAG460 and then measured the ability of the retinal cells to respond to light in the laboratory.
As mice naturally avoid light, they compared the behaviour of the blind mice in a box that had light and dark compartments before and after the injections into the retina of the light receptors and MAG460.
To more accurately assess the ability to see, the researchers created a maze for the mice. They compared the ability to exit the maze of wild mice and blind mice injected with either the light receptors and MAG460, or an inactive placebo injection.
Finally, the researchers injected a canine version of the adenovirus and light receptor mixture and MAG460 into the retinas of three blind dogs and one normal dog.
They euthanised at least one of the dogs so they could look at the retinas in the laboratory to see if the light receptors had joined to the retinal ganglion cells. They also took retinal biopsies from the other dogs to measure if the cells could respond to light.
What were the basic results?
The light receptors were successfully produced by most of the retinal ganglion cells. The chemical compound MAG460 they developed was able to cause the cells to react to blue or white light without causing retinal damage. The light receptor was also able to "switch off" in darkness.
The retinas of blind mice that had been injected with the light receptors and then MAG460 became responsive to blue and white light. The treated retinal cells were able to detect different levels of light.
After injecting the retina with light receptors and MAG460, the blind mice had a strong avoidance of the light compartment of a plastic box, similar to normal-sighted mice. This effect lasted about nine days.
The sighted mice and blind mice injected with light receptors and MAG460 were able to learn how to exit the maze with increasing speed over the course of eight days. The blind mice injected with placebo were not able to learn how to do the task.
Experiments using the retinas of dogs showed that after the injections, retinal ganglion cells produced the light receptor and this, with MAG460, was able to make these cells respond to light.
How did the researchers interpret the results?
The researchers concluded they have been able "to restore retinal light responses and enable innate and learned light-guided behaviour in blind mice".
They say the system is equally effective in the retinas of genetically engineered blind dogs when tested in the laboratory.
These results will pave "the way for extensive testing of high-resolution vision in a preclinical setting and for clinical development," they say.
This innovative set of experiments has shown retinal ganglion cells can be genetically modified to produce a receptor on their surface that can respond to light in the presence of a chemical compound called MAG460. This light receptor can be activated for up to nine days.
This was shown in laboratory experiments on the retinas of mice and dogs, and in sight-testing experiments using mice. The mice had been genetically engineered to lose both types of photoreceptors, rods and cones by 90 days.
This model mimics what occurs over a much longer timescale in the human condition retinitis pigmentosa.
It appears from this research that other cells that are not damaged in the retina, such as retinal ganglion cells, can be genetically reprogrammed to respond to light.
These experiments provide hope that, despite the original photoreceptors being damaged or dying, some function can be restored if other cells are undamaged.
This could help people with conditions such as retinitis pigmentosa, but would not be suitable for people with age-related macular degeneration or diabetic retinopathy, where the damage is more extensive.
The experiments so far show there is some ability to respond to light, but these behavioural tests are at an early stage. More sophisticated experiments are needed to further assess the extent of visual ability this process can restore.
No human trials have yet been performed, but the researchers hope this will not be too far off.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.