Out of the Dark
Breakthrough therapy helps patient see
An idea borrowed from nature is the basis for a breakthrough therapy that partially restored vision to a blind man.
The therapy uses light-sensing proteins found in bioluminescent algae.
In a paper published in May in Nature Medicine, an international team of scientists reported on this first case of partial vision recovery employing tools of a technology called optogenetics. The study marks the first time a patient has achieved functional recovery in any neurodegenerative disease with optogenetics.
Optogenetics, or manipulating proteins and cells with light, was developed in the early 2000s and 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.
“I hope it will be a major breakthrough,” says first author, José-Alain Sahel, chair of ophthalmology at the University of Pittsburgh, director of the UPMC Eye Center and professor at Sorbonne University in France. “This paper is a culmination of more than 12 years of work. I am very pleased to have contributed to this effort with Botond Roska in Basel [Switzerland] and all my colleagues at Institut de la Vision in Paris.”
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.
“The eye is a complex system that allows our vision to adapt to different levels of light,” says Sahel. “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 decided to activate the nerve cells directly.
Researchers injected the worse-seeing eye of a patient with a benign virus that carried genetic information encoding a light-sensing protein (channelrhodopsin protein ChrimsonR). These proteins, found in glowing algae, 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 the proteins, causes them to fire and transmit the signal through nerve endings to the brain.
For this study, researchers chose ChrimsonR protein because of 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 ultimately as a visible image.
The scientists figured out how to transform the light that bounces off objects in the 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 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,” says Sahel. “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 testing the technology in more people in Paris, London and Pittsburgh as COVID-19 restrictions are lifted. See “Let There Be Sight” to learn about the experience from a local trial participant’s perspective.