Behavioural responses to a photovoltaic subretinal prosthesis implanted in non-human primates

Abstract

Retinal dystrophies and age-related macular degeneration related to photoreceptor degeneration can cause blindness. In blind patients, although the electrical activation of the residual retinal circuit can provide useful artificial visual perception, the resolutions of current retinal prostheses have been limited either by large electrodes or small numbers of pixels. Here, we report the evaluation, in three awake non-human primates, of a previously reported near-infrared-light-sensitive photovoltaic subretinal prosthesis. We show that multi-pixel stimulation of the prosthesis within radiation-safety limits enabled eye tracking in the animals, that they responded to the stimulations in the direction of the implant with repeated saccades, and that the implant-induced responses were present two years after device implantation. Our findings pave the way for the clinical evaluation of a 378-electrode prosthesis in patients affected by dry atrophic age-related macular degeneration.

New Vision for Visual Prostheses

“…Early research has shown that photodiodes reliant solely on ambient light can induce neurotrophic effects, but are insufficient for phosphene generation (Chow et al, 2004;Palanker et al, 2005). By incorporating circuitry for signal amplification, significant responses were seen in animal models (Lorach et al, 2015;Prévot et al, 2019) and patients can perceive distinct phosphenes (Zrenner et al, 2010;Lorach et al, 2015). Since the image is based on incident light entering the eye instead of an externally located camera for MPDAs with electronic amplification, patients can utilize natural eye movements.…”

The primate model for understanding and restoring vision

“…Most cutting-edge therapies today are directed toward late-stage rod-cone dystrophy and atrophic or wet AMD, where loss of photoreceptors has already occurred. For this, the lack of severe inherited models displaying outer retinal loss has been compensated by the generation of acute models via laser ablation (14-16), chemically induced photoreceptor ablation (16), or the separation of the outer retina in reaction to a subretinally implanted retinal prosthesis (17). Other promising vision restoration strategies such as optogenetics have been tested extensively in normal NHPs, including marmosets (18) and macaques (19,20).…”

“…These in vitro preparations allowed us to demonstrate functional expression of genes such as microbial opsins in cone photoreceptors (70) and retinal ganglion cells (73) in the development of optogenetic therapy for restoring vision. We also used ex vivo NHP retinal explants to assess the efficacy of the PRIMA photovoltaic retinal prosthesis (17). The recent development of retinal organoids from induced pluripotent stem cells (iPSCs) has extended the interest in in vitro studies by providing an unlimited source of human retinal cells, with the additional possibility of generating tissues from patients affected by specific gene mutations (72,(74)(75)(76)(77).…”

Engineering Smart Hybrid Tissues with Built-In Electronics

“…Engineered kidneys could potentially report on the level of metabolites within the blood and whether or not they can handle their excretion. Engineered retinas could allow restoration of vision and digitization of the recorded data for various purposes (Pré vot et al, 2019). For each of these engineered tissues or organs, the lifetime of the integrated electronics could also be controlled.…”