Visual restoration by an infrared photovoltaic implant and by optogenetic therapy: validation in non-human primates

Abstract

Blindness can result from the loss of photoreceptors in retinal dystrophies or age-related macular degeneration. Electrical activation of residual retinal neurons can restore some visual function in blind patients. However, current retinal prostheses do not provide face recognition or autonomous motion in an unknown environment. To reach these goals, we have now assessed a new photovoltaic retinal prosthesis and optogenetic therapy on non-human primates for their translation towards clinical trials.

An infrared-photovoltaic implant was first assessed on an ex vivo blind primate retina using multielectrode array (MEA) recording. Many retinal ganglion cells were activated by infrared activation of a single (100μm) photovoltaic unit and not its neighbors. After an in vivo implantation, photoreceptors degenerated below the implant generating a blind spot. However, infrared stimulations of the implant induced saccades toward the implant field of view indicating visual perception.

For optogenetic therapy, living primates were injected in the vitreous with a vector to target retinal ganglion cells. On the isolated retina, application of synaptic blockers removed natural responses but ChrimsonR expressing retinal ganglion cells generated high frequency responses with a light intensity compatible with in vivo use under short term stimulations (10ms). Pattern stimulation with moving bars produced pattern of cell activations compatible with orientation detection even 6 months after the injection.

Activation of individual retinal ganglion cells and the in vivo visual perception by a single unit provide evidence for the very high resolution of the new retinal prosthesis. These prostheses are now in clinical trials for patients with dry age-related macular degeneration. For optogenetic therapy, the production of patterns of activity in retinal ganglion cells and high frequency responses with short stimuli are compatible with video rate visual stimulations. This form of optogenetic therapy is entering into clinical trials for patients with retinitis pigmentosa.

Footnotes

 This work was supported by a grant from the Franch bank of Investment (BPI France), by Pixium Vision, by Gensight Biologics, by the foundation Fighting Blindness, and by EraNet.