When the photoreceptors of the retina—the cells that sense light—are destroyed, the result is loss of vision. This is how the neurodegenerative eye disease retinitis pigmentosa (RP) results in blindness. A new study reports that a blind patient diagnosed with RP decades ago experienced partial recovery of vision thanks to a novel optogenetic treatment.
The work is the first reported case of functional recovery of vision in a neurodegenerative disease after optogenetic therapy (which controls specific cells through pulses of light, after the cells have been genetically modified to respond to such stimulation). The treatment combined gene therapy encoding the optogenetic sensor ChrimsonR with light stimulation via engineered goggles. Not only might this work help people whose eyesight is very severely impaired, it also lends support to a role in optogenetics in enabling mutation-independent, circuit-specific restoration of neuronal function in neurological diseases.
The case study is published in Nature Medicine in the article, “Partial recovery of visual function in a blind patient after optogenetic therapy.” The paper described the initial results of an ongoing Phase I/IIa study.
The work created “an artificial photosensitive layer” in a blind retina, according to Botond Roska, PhD, group leader of central visual circuits and human retinal circuit groups at the Institute of Molecular and Clinical Ophthalmology in Basel and co-senior author on the paper. To do that, they injected an adeno-associated viral vector encoding the optogenetic sensor ChrimsonR into one eye of a blind, 58-year-old male patient with RP, combined with light stimulation via engineered goggles.
In optogenetic therapy, an artificial photosensitive layer was created in the patient’s retina, which had lost all photoreceptors. This includes light sensors, from microbes, delivered to the blind retina using an injection. This gene therapy, for this patient, targeted ganglion cells of the retina.
José-Alain Sahel, MD, professor and chairman in the department of ophthalmology and co-senior author on the paper, said that the next step was to develop goggles to activate the protein. The goggles had a special camera that captured images from the visual world and transformed them into light pulses that were then projected onto the retina in real time in order to activate the modified cells during visual tasks. The light was sent into the eye like a projector in a wavelength that corresponds to the protein.
This treatment approach was well tolerated, and the previously blind patient was able to recognize, count, locate, and touch different objects with the treated eye while wearing the light-stimulating goggles.
Before treatment, the patient could not see anything with the goggles on, noted Sahel. After treatment, he added, “the patient was able to report, initially spontaneously, that he was able to see some stripes, black and white stripes on the street.” He could also see objects on a table and grasp and count the objects.
Importantly, it was possible to show that visual behavior was correlated with brain activation corresponding to visual function.
The authors concluded that optogenetic therapy may be beneficial in restoring visual function in people with RP-related blindness. However, further results from this trial are needed for a clearer picture of the safety and efficacy of this approach.
This result has been, Roska noted, the result of a 13-year collaboration between his group and colleagues at the University of Pittsburgh school of medicine, led by Sahel.
“This exciting new technology might help people whose eyesight is very severely impaired,” notes James Bainbridge, PhD, professor of retinal studies at University College London. He added that this high-quality study, which is carefully conducted and controlled, is based on laboratory tests in just one individual. “Further work,” he asserted, “will be needed to find out if the technology can be expected to provide useful vision.”