Partial recovery of visual function in patients with visual impairment after optogenetic treatment
Optogenetics may allow for circuit-specific recovery of neural function independent of mutations in neurological diseases. Retinitis pigmentosa is a neurodegenerative eye disease in which loss of photoreceptors can lead to complete blindness. In patients with visual impairment, we combined intraocular injection of an adeno-associated viral vector encoding ChrimsonR with light stimulation via manipulated goggles. The goggles detect local changes in light intensity and project the corresponding light pulses into the retina in real time to activate optogenetically converted retinal ganglion cells. Patients recognized, identified, counted, and made contact with a variety of objects while wearing goggles, using only their vector-processed eyes. During the vision, multi-channel EEG recordings revealed object-related activity over the visual cortex. Patients were unable to visually detect objects before injection with or without goggles, or after injection without goggles. This is the first reported example of partial functional recovery in a neurodegenerative disease after optogenetic treatment.
Sahel, JA., Boulanger-Scemama, E., Pagot, C., et al. Partial recovery of visual function in patients with visual impairment after optogenetic treatment. Nat Med (2021). https://doi.org/10.1038/s41591-021-01351-4
Commentary
This study provides the first evidence that injection of an optogenetic sensor-expressing gene therapy vector combined with the wearing of light-stimulating goggles can partially restore visual function in RP patients who had light perception-only vision.
The results of three visual and visuomotor tests suggested that photogenetic retinal stimulation induced vision, and that the visual processes leading to perception were effective enough to allow the patient to turn toward an object and perform the visuomotor task of reaching it.
In addition to visual and visuomotor tests, further evidence of visual recovery was obtained in that EEG recordings of occipital cortex signals were modulated by the presence or absence of visual objects.
In this study, EEG recordings suggested that retinal activity induced by photogenetic stimulation of the retina propagates to the primary visual cortex and modulates its activity.The three visual tests were performed in an indoor lab according to a pre-established protocol. They also examined the patients' ability to recognize patterns while out on the street. In the results, in the stimulated monocular condition rather than the natural binocular condition, the patient reported that he spontaneously identified crosswalks and he could count the number of white stripes. And only when using the goggles, he testified that his daily visual activities were greatly improved, such as detecting plates, mugs, and telephones; detecting furniture in a room; and detecting doors in a hallway.
Thus, treatment with a combination of photogenetic vectors and photostimulation goggles could have led to a level of visual recovery for this patient that would have meaningful benefits for his daily life.
The red fluorescent protein tdTomato encoded by these injected vectors could, in theory, be visualized by a scanning laser ophthalmoscope, but visualization of the red fluorescent probe using a scanning laser ophthalmoscope has not yet been approved for clinical use.
