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

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 multipixel stimulation of the prosthesis within radiation safety limits enabled eye tracking in the animals, that they responded to stimulations directed at 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 the prosthesis in patients affected by dry atrophic age-related macular degeneration. A near-infrared-light-sensitive photovoltaic subretinal prosthesis triggers behavioural responses in awake macaques, even two years after device implantation.

[1]  K W Horch,et al.  Reading speed with a pixelized vision system. , 1992, Journal of the Optical Society of America. A, Optics and image science.

[2]  Angélica Pérez Fornos,et al.  Simulation of artificial vision: IV. Visual information required to achieve simple pointing and manipulation tasks , 2008, Vision Research.

[3]  F. Werblin,et al.  A method for generating precise temporal patterns of retinal spiking using prosthetic stimulation. , 2006, Journal of neurophysiology.

[4]  H. Lorach,et al.  Retinal safety of near infrared radiation in photovoltaic restoration of sight. , 2016, Biomedical optics express.

[5]  B. Jones,et al.  Retinal Remodeling and Metabolic Alterations in Human AMD , 2016, Front. Cell. Neurosci..

[6]  S. Schein,et al.  A four-surface schematic eye of macaque monkey obtained by an optical method , 1995, Vision Research.

[7]  U. Leonards,et al.  Simulation of artificial vision: I. Eccentric reading of isolated words, and perceptual learning , 2003, Vision Research.

[8]  A. Sher,et al.  Photovoltaic restoration of sight with high visual acuity , 2015, Nature Medicine.

[9]  Sébastien Joucla,et al.  Improved Focalization of Electrical Microstimulation Using Microelectrode Arrays: A Modeling Study , 2009, PloS one.

[10]  Lauren N Ayton,et al.  Progress in the clinical development and utilization of vision prostheses: an update , 2016, Eye and brain.

[11]  Joseph F Rizzo,et al.  Encoding visual information in retinal ganglion cells with prosthetic stimulation , 2011, Journal of neural engineering.

[12]  Jessy D. Dorn,et al.  The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss , 2013, British Journal of Ophthalmology.

[13]  A. Sher,et al.  Photovoltaic Retinal Prosthesis with High Pixel Density , 2012, Nature Photonics.

[14]  S. E. Hughes,et al.  Transplantation of photoreceptors to light-damaged retina. , 1989, Investigative ophthalmology & visual science.

[15]  R. Jensen,et al.  Thresholds for activation of rabbit retinal ganglion cells with relatively large, extracellular microelectrodes. , 2005, Investigative ophthalmology & visual science.

[16]  S. Picaud,et al.  GABAA and GABAC receptors in adult porcine cones: evidence from a photoreceptor‐glia co‐culture model , 1998, The Journal of physiology.

[17]  Ryad Benosman,et al.  Synthetic 3D diamond-based electrodes for flexible retinal neuroprostheses: Model, production and in vivo biocompatibility. , 2015, Biomaterials.

[18]  Richard A. Normann,et al.  Simulation of a phosphene-based visual field: Visual acuity in a pixelized vision system , 2006, Annals of Biomedical Engineering.

[19]  B. Rappaz,et al.  Simulation of artificial vision: II. Eccentric reading of full-page text and the learning of this task , 2004, Vision Research.

[20]  Yitzhak Yitzhaky,et al.  Active confocal imaging for visual prostheses , 2015, Vision Research.

[21]  P H Schiller,et al.  The effects of lateral geniculate nucleus, area V4, and middle temporal (MT) lesions on visually guided eye movements , 1994, Visual Neuroscience.

[22]  Albrecht Rothermel,et al.  Interim Results of a Multicenter Trial with the New Electronic Subretinal Implant Alpha AMS in 15 Patients Blind from Inherited Retinal Degenerations , 2017, Front. Neurosci..

[23]  E. Callaway,et al.  Anatomical Identification of Extracellularly Recorded Cells in Large-Scale Multielectrode Recordings , 2015, The Journal of Neuroscience.

[24]  D. Palanker,et al.  Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes , 2014, Journal of neural engineering.