Using a protein found in algae, a new technology partially restored the sight of a completely
blind man.
He can now locate, identify and count objects using the treated eye while wearing specialized
goggles.
Optogenetic therapy, or manipulating proteins and cells with light, is an advanced technology
developed in the early 2000s that drove major discoveries about the inner workings of our
brains.
Yet, while actively researched in experimental animals, functional improvement using this
method was never reported in humans—until now.
In a paper published in the journal Nature Medicine, scientists from Paris, Pittsburgh
and Basel, Switzerland, reported the first-ever case of partial vision recovery in a blind
patient after optogenetic therapy.
The pioneering study describes the first time a patient has achieved partial functional
recovery in any neurodegenerative disease by using optogenetic tools.
The researchers hope it will be a major breakthrough.
The paper describes the progress of a patient in Paris who 40 years ago was diagnosed with
retinitis pigmentosa—a progressive neurodegenerative disease that destroys light-sensitive cells
in the retina and leads to complete blindness.
Retinitis pigmentosa is caused by mutations in more than 71 different genes—so developing
gene therapies to replace a few proteins to repair broken cellular machinery is challenging
and not very effective.
The eye is a very complex system that allows our vision to adapt to different levels of
light.
But complex systems are very fragile—so when vision disappears, there are few treatments
left aside from using prosthetics or reactivating remaining cells in the retina.
So, the researchers approached the problem from a completely different angle—rather
than fixing mutated genes one-by-one in cells that respond to light by activating nerve
cells in the retina, they decided to activate the nerve cells directly.
That is where optogenetic tools come in.
For this study, researchers injected the worse-seeing eye of a patient with an adenovirus-associated
vector that carried genetic information encoding a light-sensing protein called channelrhodopsin
protein ChrimsonR.
Channelrhodopsin proteins, which are found in glowing algae in nature, respond to light
by changing their shape and allowing the flow of ions in and out of the cells.
The flow of ions activates the cells and, in the case of neurons experimentally engineered
to express channelrhodopsins, causes them to fire and transmit the signal through nerve
endings to the brain.
For this study, researchers chose ChrimsonR protein for its preference for activation
by amber-colored light, which is safer and causes less pupil constriction than blue-spectrum
light, like that from computer screens.
The construct targeted ganglion cells of the retina—neurons that collect signals from
cones and rods and transfer them through the optic nerve to the brain, where that information
is processed to be perceived as a visible image.
To activate the ganglion cells this way, the scientists had to come up with a way to transform
the light that bounces off objects in our environment to a single wavelength in the
amber spectrum.
To do that, researchers used special goggles equipped with a camera that detects changes
in light intensity pixel by pixel as distinct events.
The transformed image from the camera is then projected as discrete light pulses onto the
retina in real time, like a movie projector onto a theater screen.
The results were remarkable.
After a period of adjusting and learning how to use the technology, the patient was able
to locate, identify and count different objects using the treated eye while wearing the goggles.
The patient could not visually detect any objects before the injection or without the
goggles after the injection.
Adjusting to using the glasses takes time.
Initially, the patient didn’t find the glasses very useful, but after a few months, he started
to see the white stripes on a crosswalk and after several training sessions was able to
recognize other objects, big and small.
The researchers are hoping to start testing the technology in more people in Paris, Pittsburgh
and London as soon as COVID-19 restrictions are lifted.