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Paul-Henri PREVOT, Marion Lanoë, Sami Dalouz, Kévin BLAIZE, Omar Oubari, Kevin Gehere, Himanshu Akolkar, Guillaume Buc, Serge A Picaud, Jose Alain Sahel; Behavioral and electrophysiological characterization of photovoltaic subretinal implants in non-human primates. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4270.
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Subretinal photovoltaic implants were shown to elicit neural responses in blind rodents at the retinal and cortical levels. To prepare their translation to clinic, we have investigated their efficacy by ex vivo tests on blind non-human primate retinas and by in vivo behavioral tests in three implanted non-human primates.
Photoreceptors were shaved off from the non-human primate retina by vibratome sectioning. The resulting blind inner retina was recorded on a multielectrode array (MEA) while concurrently activating the implant with IR pulses. Three non-human primates (Macaqua fascicularis) were implanted with one prosthesis (100 or 140 µm pixel size). Saccadic tasks were taught to the primates using visible stimulations on a custom-made stimulation platform allowing visible and IR stimulations (880nm).
RGCs responded reliably ex vivo to full-field stimulation (500µW.mm-2 at 4ms) and to single 100µm-wide pixel activation. (3-4 mW.mm-2 at 4ms). Application of synaptic blockers showed that this activity resulted from the stimulation of bipolar cells. Subsequently, we developed the surgery on non-human primates to prepare clinical trials. In vivo imaging indicated an expected photoreceptor degeneration at the implant location due to lack of nutriment access from the RPE, creating a blind spot for visible stimulations. In behavioral tests, already one primate (100µm pixel) reliably responded to IR stimulations above the implant. The threshold parameters required to elicit with 50% chance a successful saccade were the following: 175-200µm stimulations, 200µW.mm-2 intensity, 2-3 ms pulse widths and 2 successive flashes. Natural responses to infrared light were ruled out through several controls.
These results demonstrate that our photovoltaic subretinal implants can stimulate indirectly retinal ganglion cells in the degenerated primate retina. The spatial resolution was at the single cell pixel resolution in both ex vivo and in vivo tests. These results pave the way for clinical trials.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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