Optogenetic therapy
Optogenetics helped partially restore a man's vision after 40 years of blindness
Anastasia Kuznetsova, N+1
Neuroscientists partially restored the sight of a man who had been blind for 40 years. To do this, they applied optogenetic therapy: with the help of viral vectors, genes encoding a photosensitive ion channel were delivered to retinal ganglion cells. With the help of glasses projecting light waves onto the retina, the man began to distinguish objects in front of him. Before that, retinitis pigmentosa was considered an incurable disease. The article was published in Nature Medicine (Sahel et al., Partial recovery of visual function in a blind patient after optogenetic therapy).
Retinitis pigmentosa is a hereditary degenerative eye disease associated with 71 mutations of various genes. Retinal photoreceptors are damaged in sick people. First, the patient loses the ability to see at dusk, peripheral vision degrades, and then complete blindness may occur. At the moment, there are about two million people living with this disease in the world. To date, there has been no cure for it, although they have tried to use stem cells, cannabinoids and gene therapy.
Optogenetic vision restoration is an innovative therapy for the treatment of retinitis pigmentosa. It became possible thanks to the discovery of opsins – photosensitive channels that cause depolarization or hyperpolarization of the cell through the influx of ions. Using different wavelengths, neurons can be manipulated by opening and closing ion channels. Previously, with the help of optogenetics methods, scientists were able to restore vision in macaques. Viral vectors with genes encoding opsin were injected into the ganglion layer of the retina. As a result, the nerve impulse from the light hitting the modified ganglion cells completely coincided with the one emitted by ordinary ones when stimulated from rods and cones. Unfortunately, it was impossible to evaluate the image seen by the monkey, but this experiment showed the possibilities of optogenetics in restoring vision.
The scientific group of Botond Roska from the University of Basel has been collaborating for 13 years with the group of José-Alain Sahel from the Sorbonne University to make possible an operation for optogenetic restoration of vision in humans. "The retina is a biological computer in the eyes. In the upper layer there are photosensitive cells, and in the lower layer there are ganglion cells that form the optic nerve. In patients with retinitis pigmentosa, only the upper layer is damaged. By acting on ganglion cells, we have created an artificial layer of light–sensitive cells in the retina of a blind person," Botond Roska says about the work done.
Scientists have applied the method of optogenetic vision restoration in a man who lost his sight 40 years ago and perceived only the difference between light and darkness. They used an adenoviral vector encoding the opsin ChrimsonR coupled to the fluorescent protein tdTomato. This design increases the embedding of ChrimsonR into the cell membrane. The vector was injected into the ganglion cells of the retina of the eye, which saw worse. Scientists put camera glasses on the patient, which record the change of light in each pixel, transform the light into monochrome images and send it to the retina like a projector. These light waves activate the opsins of the retinal ganglion cells, and a signal from them enters the brain.
After the procedure, the man distinguished the objects lying on the table in front of him (in 92 percent of cases), and was also able to count them (in 63 percent of cases).
To assess neural activity, the patient underwent electroencephalographic examination. The greatest activity when viewing objects was observed in the occipital cortex on the opposite side of the eye, in which vision was partially restored.
A patient during one of the tests. Figure from the article Sahel et al.
"The patient needs time to adapt to the new signals coming from the eye, since these signals, despite all the efforts of scientists, are still not natural for the body. At first, the patient saw flashes, and then a "starry sky". Improvements are coming gradually," Sahel concluded. The patient was not blind in childhood, so scientists hope that the adaptation process will not take much time due to the memory of visual images preserved in the brain.
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