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Optogenetic Therapy to Give the Blind Vision
Optogenetics is a scientific discipline involving the genetic modification of neurons to render them sensitive to certain wavelengths of light.
Retinitis pigmentosa (RP) is an inherited blinding disease caused by mutations in more than 71 different genes, and affecting more than 2 million people globally.
Optogenetic vision restoration is a mutation-independent approach for restoring visual function at the late stages of RP after vision is lost. The treatment combines combines retinal injection of an optogenetic vector with wearing light-stimulating goggles.
This vector encoding the light-sensing protein, ChrimsonR, fused to the red fluorescent protein, tdTomato, was administered by an injection into the retina of the worse-seeing eye to target mainly foveal retinal ganglion cells.
The light-stimulating goggles capture images from the visual world using a neuromorphic camera that detects changes in intensity, pixel by pixel, as distinct events. The goggles then transform the events into monochromatic images and project them in real time as light pulses onto the retina.
The light-stimulating goggles were tested on the patient three times before the retinal injection and the patient did not report any change of vision. The patient underwent systematic visual training using the light-stimulating goggles. Seven months after the start of visual training, the patient began to report signs of visual improvement when using the goggles.
The patient’s first test involved perceiving, locating and touching a single object placed on a white table. He did so under three conditions: (1) both eyes open without the light-stimulating goggles (natural binocular), (2) untreated eye covered, treated eye open without the goggles (natural monocular), and (3) untreated eye covered, treated eye open and stimulated with the goggles (stimulated monocular).
In this test, the patient was unable to perceive any of the objects under natural binocular or natural monocular conditions. However, in the stimulated monocular condition, wherein the treated eye was stimulated with goggles, the patient perceived the presence of, located and touched the large object in 92% (36 out of 39) of the trials.
It was noted that once the object was perceived, the patient could coordinate his motor system with the percept. In a second test, the patient was asked to determine how many objects were placed on the white table and point to them without touching. Each object was positioned in 1 of 6 possible positions.
In this test, similar to the results of the first test, the patient was unable to perceive the objects without the light-stimulating goggles. However, in the stimulated monocular condition, the patient perceived the objects in 63% of the trials (12 out of 19). Furthermore, he correctly counted and located them in most of the trials (count, 63% (12 out of 19); locate, 58% (11 out of 19).
This experiment provides evidence that the injection of an optogenetic gene therapy vector combined with the wearing of light-stimulating goggles can partially restore visual function in a patient. Furthermore, the EEG (electroencephalogram) recording of the patient’s occipital cortex signals was modulated by the presence or absence of a visual object indicating the presence of its visual perception in the brain.