Optogenetics Restores Partial Sight to Blind Patient

Article: For the First Time, Optogenetic Therapy Partially Restores Patient’s Vision
Source: University of Pittsburgh Medical Center
Article: Optogenetic Methods Restore Partial Vision in a Blind Patient
Source: Sorbonne University (France)
Article: Gene therapy restores partial vision to a blind patient
Source: University of Basel (Switzerland)
Published: May 24, 2021

Optogenetics has origins in neuroscience as a method using light to turn neurons "on" and "off" in order to investigate their function. In this case, the same principles are applied to turn retinal ganglion cells (RGCs) on and off in a blind patient with retinitis pigmentosa (RP), an inherited condition that results in degeneration of the photoreceptors upstream from the retinal ganglion cells. The optogenetic therapy in this case used channelrhodopsin (ChrimsonR), an optogenetic sensor originally derived from algae with a red-shifted action spectrum that responds to amber light rather than blue light, the former being safer and causes less pupil constriction. The light source comes from a pair of goggles with a neuromorphic camera that captures and projects pulses of 595 nm amber-colored light onto the retina to activate the ChrimsonR proteins. Pulses of light are necessary as a stimulus because RGCs respond to changes in light. The gene therapy was delivered by intravitreal injection of adeno-associated viral vectors in the patient's worse-seeing eye. As the anterior-most layer of the retina and the most resilient type of retinal cells, retinal ganglion cells are the easiest target for gene therapy (e.g., by intravitreal injection); however, the researchers are also experimenting with inserting optogenetic proteins into bipolar cells and dormant cones.

Electroencephalography (EEG) data

With the light-stimulating goggles, and after visual rehabilitation to familiarize his brain with how to interpret the new information coming from the light pulses, the patient was able to locate different objects placed on a table when tested in the lab. Because the retina contains around 100 times more photoreceptors than it does RGCs, the image resolution detected by RGCs as a "starry sky" of amber-colored dots will never be as good as natural vision. However, electroencephalography during the lab tests confirmed that visual behavior correlated with activation of the primary visual cortex. The patient also reports being able to count the number of stripes on a pedestrian crosswalk outdoors. And as the researchers note in the paper, "[T]he patient testified to a major improvement in daily visual activities, such as detecting a plate, mug or phone, finding a piece of furniture in a room or detecting a door in a corridor but only when using the goggles." This form of gene therapy takes months to take effect in the retina, and months further for the brain to essentially learn a new language, but the visual gains appear to have a positive effect on the patient's quality of life.

Although retinitis pigmentosa encompasses a variety of genetic mutations, what is promising about using optogenetics to activate RGCs is that it is a mutation-independent treatment strategy and could be a potential treatment for neurodegenerative photoreceptor diseases beyond RP. The patient in question is the first in the PIONEER clinical trial, a three dose-escalation study to determine the safety of the optogenetic gene therapy. This patient received the lowest dose, and the researchers hope to see even better results with the higher doses. An alternative treatment for such patients are devices that send signals from a camera mounted on a pair of glasses to electrodes implanted in the retina; however, this method has the disadvantage of requiring surgery compared to intraocular injection. Though the gain of sight with optogenetic therapy will likely remain limited without enough resolution to recognize faces or read, nor the ability to perceive color, this milestone proof-of-concept demonstrates the potential of optogenetics in visual restoration and rehabilitation.

Additional note : Because the patient's vision prior to the gene therapy included light perception, a critique that was raised was that because light stimulation training with amber-color light with the goggles was not conducted prior to the treatment, it is not certain whether that would be enough to allow him to see or if the therapy itself was solely responsible for his change in vision.

My rating of this study: ⭐⭐⭐⭐⭐

Sahel J, Boulanger-Scemama E, Pagot C, et al. "Partial recovery of visual function in a blind patient after optogenetic therapy." Nature Medicine.  24 May 2021. https://doi.org/10.1038/s41591-021-01351-4

Additional reference articles:
Article: Optogenetic Therapy Partially Restores Vision in a Blind Patient
Source: Technology Networks
Article: Gene Therapy Partially Restores Vision in Blind Patient in First Case of Its Kind
Source: ScienceAlert
Article: A gene-based therapy partially restored a blind man’s vision
Source: Science News Magazine
Article: Blind Patient Recovers Partial Vision with Optogenetics
Source: The Scientist
Article: Blind man regains some vision, with help from light-sensing algal protein
Source: Science
Article: Injection of light-sensitive proteins restores blind man’s vision
Source: Nature
Article: Scientists Partially Restored a Blind Man’s Sight With New Gene Therapy
Source: New York Times
Published: May 24, 2021
Article: In a First, Optogenetics Leads to Partial Recovery of Vision for Blind Patient
Source: Genetic Engineering & Biotechnology News
Published: May 25, 2021
Article: A Closer Look at Optogenetics: Bringing Hope to People with Vision Impairment
Source: Sorbonne University (France)
Published: June 3, 2021