Photovoltaic retinal prosthesis restores high-resolution responses to single-pixel stimulation in blind retinas

Retinal prostheses hold the promise of restoring vision in totally blind people. However, a decade of clinical trials highlighted quantitative limitations hampering the possibility of reaching this goal. A key challenge in retinal stimulation is to independently activate retinal neurons over a large portion of the subject’s visual field. Reaching such a goal would significantly improve the perception accuracy in retinal implants’ users, along with their spatial cognition, attention, ambient mapping and interaction with the environment. Here we show a wide-field, high-density and high-resolution photovoltaic epiretinal prosthesis for artificial vision (POLYRETINA). The prosthesis embeds 10,498 physically and functionally independent photovoltaic pixels, allowing for wide retinal coverage and high-resolution stimulation. Single-pixel illumination reproducibly induced network-mediated responses from retinal ganglion cells at safe irradiance levels. Furthermore, POLYRETINA allowed response discrimination with a high spatial resolution equivalent to the pixel pitch (120 µm) thanks to the network-mediated stimulation mechanism. This approach could allow mid-peripheral artificial vision in patients with retinitis pigmentosa.

Photovoltaic stimulation of retinal microcircuit for vision restoration

Naïg Aurelia Ludmilla Chenais

Sight restoration through retinal prostheses was still a mere dream a century ago. Current challenges are even greater: providing a quantitatively and qualitatively useful artificial vision to late blind patients. Existing approaches all face engineering and biological questions which directly threaten the quality of the restored vision. Compromises made on stiff materials or external powering restrain the restored visual field and the stimulation resolution. Epiretinal implants are large but offer limited resolution, and stimulate retinal ganglion cell non-specifically through multiple compartments, including distal axons. Subretinal and suprachoroidal implants are limited in size but rely on inner retina activation: it allows to preserve most of spatial and temporal properties of the sighted response, but neurons' responsivity rapidly wanes. Axonal activation and desensitization hamper the spatiotemporal properties of the perceived phosphenes. High-level perceptual mechanisms can resolve the missing piece of information, but require a high cognitive load: a too high price to pay for implants recipients to adapt and use artificial vision on day to day life. Current visual prostheses do not rescue vision as a primary sense in implanted patients. A 20/200 visual acuity, together with a 30 to 40° visual field and qualitative properties as close as possible to patients' early visual experience are the minimal requirements for a useful prosthetic approach. The introduction of light-powered electronics represents a step forward in biomimetic retinal activation, but it is not fully emancipated from power supply and limited coverage concerns. The use of organic semiconductors allows to fabricate flexible p-n junctions that can be embedded into a large hemispherical epiretinal implant. Such a photovoltaic array can cover 45° of visual angle, and total up to 10'498 pixels. Complementary to this high-density and wide-field implant engineering, investigations on retinal network activation allow to design network-oriented photovoltaic stimulation paradigms. Strategies that factor the intrinsic connectivity and properties of retinal neurons - convergence, lateral inhibition and adaptation mechanisms - permit to take advantage of the retinal microcircuit organization. A wide-field photovoltaic epiretinal approach could restore peripheric vision with native visual acuity in Retinitis Pigmentosa patients, as well as a theoretical 20/480 foveal visual acuity. The high resolution of the stimulation has been electrophysiologically evaluated in-vitro; photovoltaic stimulation of degenerating mouse retinas revealed that the non-rectangular photovoltage delivered under 560 nm illumination was prone to recruit inner excitatory and inhibitory circuits from the epiretinal side. This allows first to avoid uncontrolled axonal stimulation of retinal ganglion cells, second to preserve the intrinsic processing, and third to benefit from natural lateral response segregation. In addition, delivering light stimuli in a non-stationary manner that micmics fixational saccades allows to reduce neurons' desensitization. The proposed approach, that combines withstanding organic photovoltaic prosthesis, and naturalistic epiretinal stimulation paradigm, could allow to stimulate human parasol cells with a natural spatial resolution and limit the need of head scanning. Both points are critical for motion perception, self-orientation and ambulation in late blind patients.

EPFL2021

Naturalistic spatiotemporal modulation of epiretinal stimulation increases the response persistence of retinal ganglion cell

Marta Jole Ildelfonsa Airaghi Leccardi, Naïg Aurelia Ludmilla Chenais, Diego Ghezzi

Objective. Retinal stimulation in blind patients evokes the sensation of discrete points of light called phosphenes, which allows them to perform visually guided tasks, such as orientation, navigation, object recognition, object manipulation and reading. However, the clinical benefit of artificial vision in profoundly blind patients is still tenuous, as several engineering and biophysical obstacles keep it far away from natural perception. The relative preservation of the inner retinal neurons in hereditary degenerative retinal diseases, such as retinitis pigmentosa, supports artificial vision through the network-mediated stimulation of retinal ganglion cells. However, the response of retinal ganglion cells to repeated electrical stimulation rapidly declines, primarily because of the intrinsic desensitisation of their excitatory network. In patients, upon repetitive stimulation, phosphenes fade out in less than half of a second, which drastically limits the understanding of the percept. Approach. A more naturalistic stimulation strategy, based on spatiotemporal modulation of electric pulses, could overcome the desensitisation of retinal ganglion cells. To investigate this hypothesis, we performed network-mediated epiretinal stimulations paired to electrophysiological recordings in retinas explanted from both male and female retinal degeneration 10 mice. Main results. The results showed that the spatial and temporal modulation of the network-mediated epiretinal stimulation prolonged the persistence of the retinal ganglion cell's response from 400 ms up to 4.2 s. Significance. A time-varied, non-stationary and interrupted stimulation of the retinal network, mimicking involuntary microsaccades, might reduce the fading of the visual percept and improve the clinical efficacy of retinal implants.

2020

Photovoltaic stimulation of retinal microcircuit for vision restoration

Naïg Aurelia Ludmilla Chenais

EPFL2021

Naturalistic spatiotemporal modulation of epiretinal stimulation increases the response persistence of retinal ganglion cell

Marta Jole Ildelfonsa Airaghi Leccardi, Naïg Aurelia Ludmilla Chenais, Diego Ghezzi

2020