Just like plants on land, algae in water uses sunlight as an energy source. This mechanism varies between species but is generally made up of a light-sensing system of photoreceptors and light-modulated signalling pathways. This allows the plants to perceive light and more toward or away from it as needed.
Now, these light-sensing algae proteins have been used to partially restore the vision of a completely blind man, using a technique known as optogenetics.
Optogenetics is a biological process where light-sensing molecules are added to brain cells. The tool is relatively new to medicine but has been a mainstay of neuroscientific experiments on animals for many years. Using light pulses from fibreoptic cables, researchers can then trigger specific nerves to fire and even induce specific kinds of behaviour.
The 58-year-old man, who has not been identified, has a neurodegenerative visual impairment known as retinitis pigmentosa (RP). RP is a cluster of genetic visual impairments, which all lead to the breakdown of cells in the retina, light-sensitive tissue that lines the back of the eye.
RP gradually causes night blindness, loss of peripheral and central vision and trouble seeing different colours. The condition affects roughly one in 4,000 people worldwide and can sometimes lead to complete blindness, as it did in this case. It can be triggered by abnormalities in any one of over 50 genes.
Optogenetics: a study in ChrimsonR
The research was led by Dr José-Alain Sahel, a world expert in retinal diseases and vision restoration. Sahel and his team used light-sensing channelrhodopsin proteins found in the Chlamydomonas noctigama algae, a freshwater species native to marshes in Russia, to partially restore the man’s capacity for sight.
To achieve this, scientists inserted the genetic code for a light-sensing protein into a virus modified to be harmless, then injected the modified viral vector into the retinal ganglion cells of the man’s weakest eye.
The protein they used, ChrimsonR, reacts most strongly to colours at the redder end of the spectrum, especially amber light. Researchers chose this protein for the experiment because amber light is understood to be safer and causes less pupil constriction than the blue light used to activate other sensors. ChrimsonR was also fused to the red fluorescent protein tdTomato, to increase its expression in the cell membrane.
With the proteins in place, r the research team hoped that when hit with light, the ChrimsonR cells would send electrical signals to the brain and allow the patient to perceive it. However, the patient wasn’t simply sent out into the world and asked to report back if anything in his vision changed – instead, the researchers relied upon a novel medical device to test their work.
Light-stimulating goggles were employed to test whether or not the therapy had worked. The goggles are designed to pick up changes in the intensity and contrast of light in the surrounding environment and then project a corresponding amber image onto the retina at high intensity using the specific wavelength that triggers ChrimsonR.
The goggles were tested three times on the patient before the vector injection, with the patient reporting no change of vision or light sensitivity on any of these occasions.
Four and a half months after the injection, researchers then started systematic visual training of the patient using the goggles. They waited this long because the expression of ChrimsonR-tdTomato in the ganglion cells wasn’t seen to stabilise until two to six months after injection in non-human primates during prior trials.
However, the patient didn’t see report any signs of visual improvement when using the goggles until seven months into visual training – meaning it was almost a year after the injection that a positive change was seen.
Now, the patient has been able to perceive, locate, count and touch different objects while wearing the goggles. The man was able to perceive whether a notebook had been placed on the table in front of him and could count dark-coloured cups set out before him – although not always accurately.
But perhaps the most exciting aspect of this is the therapy’s real-world impact. As well as being able to perceive objects when wearing the goggles during lab tests, the patient has reported being able to see the white lines of a pedestrian crossing when out on a walk, without having to wear the goggles at all.
Sahel told the BBC: “This patient initially was a bit frustrated because it took a long time between the injection and the time he started to see something.
“But when he started to report he was able to see the white stripes to come across the street you can imagine he was very excited. We were all excited.”
The patient’s vision has since improved with further training, although it is far from fully restored and he is unable to recognise faces.
Still, the findings of the study are the first concrete proof that optogenetics could be used to, at least partially, restore a patient’s lost vision. Several patients have now gone on to receive the same injection, but due to Covid-19 related delays no one else has been able to train with the goggles so far.
Other uses of optogenetics
The optogenetics market is currently surging, with Fact.MR estimating that revenues will nearly double over the next ten years with a five-year compound annual growth rate of 17%.
As well as helping to restore sight, optogenetics has demonstrated potential applications in treating Parkinson’s disease and hearing loss.
In December last year, Maplight received an $8.1m grant from the Michael J. Fox Foundation for Parkinson’s Research to tackle the symptoms of anxiety and depression in Parkinson’s disease using optogenetics.
The technique will be used to identify brain regions related to emotional control and motor function, which may be damaged during the course of the disease and lead to the development of these symptoms. A Parkinson’s model will then be used to confirm the circuits’ link to anxiety and depression.
Researchers are also working on optogenetic cochlear implants that can recreate auditory signals for people with hearing loss. The primary neurons in the ear, spiral ganglion neurons, may be able to be modified to make them sensitive to light.
If this proves possible, an optogenetic-based cochlear implant may be able to convert auditory information into a light-based signal and stimulate the brain in a similar way to if it were stimulated by the electrical pulses of a conventional cochlear implant.
An optogenetic cochlear implant could provide an improved hearing experience for the user, as the sound stimulation could be much more focused than through the limited electric current cochlear implants can currently apply.