Restoring vision to the blind has been an objective of several research teams for a number of years. It is known that spots of light -- phosphenes -- can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this, however, our understanding of prosthetic vision remains rudimentary. To advance the realisation of a clinically viable prosthesis for the blind, a versatile integrated circuit neurostimulator was designed, manufactured, and verified. The neurostimulator provides electrical stimuli to surviving neurons in the visual pathway, affording blind patients some form of patterned vision; besides other benefits (independence), this limited vision would let patients distinguish between day and night (resetting their circadian rhythm). This thesis presents the development of the neurostimulator, an interdisciplinary work bridging engineering and medicine. Features of the neurostimulator include: high-voltage CMOS transistors in key circuits, to prevent voltage compliance issues due to an unknown or changing combined tissue and electrode/tissue interface impedance; simultaneous stimulation using current sources and sinks, with return electrodes configured to provide maximum charge containment at each stimulation site; stimuli delivered to a two dimensional mosaic of hexagonally packed electrodes, multiplexing current sources and sinks to allow each electrode in the whole mosaic to become a stimulation site; electrode shorting to remove excess charge accumulated during each stimulation phase. Detailed electrical testing and characterisation verified that the neurostimulator performed as specified, and comparable to, or better than, other vision prostheses neurostimulators. In addition, results from several animal experiments verified that the neurostimulator can elicit electrically evoked visual responses. The features of the neurostimulator enable research into how simultaneous electrical stimulation affects the visual neural pathways; those research results could impact other neural prosthetics research and devices.

Restoring vision to the blind has been an objective of several research teams for a number of years. It is known that spots of light -- phosphenes -- can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this, however, our understanding of prosthetic vision remains rudimentary. To advance the realisation of a clinically viable prosthesis for the blind, a versatile integrated circuit neurostimulator was designed, manufactured, and verified. The neurostimulator provides electrical stimuli to surviving neurons in the visual pathway, affording blind patients some form of patterned vision; besides other benefits (independence), this limited vision would let patients distinguish between day and night (resetting their circadian rhythm). This thesis presents the development of the neurostimulator, an interdisciplinary work bridging engineering and medicine. Features of the neurostimulator include: high-voltage CMOS transistors in key circuits, to prevent voltage compliance issues due to an unknown or changing combined tissue and electrode/tissue interface impedance; simultaneous stimulation using current sources and sinks, with return electrodes configured to provide maximum charge containment at each stimulation site; stimuli delivered to a two dimensional mosaic of hexagonally packed electrodes, multiplexing current sources and sinks to allow each electrode in the whole mosaic to become a stimulation site; electrode shorting to remove excess charge accumulated during each stimulation phase. Detailed electrical testing and characterisation verified that the neurostimulator performed as specified, and comparable to, or better than, other vision prostheses neurostimulators. In addition, results from several animal experiments verified that the neurostimulator can elicit electrically evoked visual responses. The features of the neurostimulator enable research into how simultaneous electrical stimulation affects the visual neural pathways; those research results could impact other neural prosthetics research and devices.

L’objectif de cette thèse est la validation fonctionnelle d’implants rétiniens pour la restauration fonctionnelle de la vision chez des patients non voyants suite à la perte de leurs photorécepteurs. Ce travail a été réalisé sur modèle animal et a évalué expérimentalement de nouveaux protocoles de stimulation. Tout d’abord nous avons utilisé la technique de spectroscopie d’impédance pour simuler mathématiquement l’interface tissu-implantafin de caractériser la présence d’un espace entre le tissu et l’implant. La seconde partie compare par imagerie optique (IO) les caractéristiques de la réponse corticale évoquée par stimulation visuelle ou électrique de la rétine par prothèse sous rétinienne. Nous avons retrouvé que la taille de l’activation par l’implant rétinien est beaucoup plus grande que son correspondant visuel. Dans une troisième partie, est réalisée une évaluation in vitro de la performance des stimulations sur rétine isolée pour définir comment les cellules ganglionnaires réagissent à différents modes de stimulations. Ce travail a permis d’établir la courbe des réponses en fonction de l’intensité des stimulations électriques. Enfin, la thèse décrit un modèle animal de dégénérescence rétinienne qui présente des désorganisations de la rétine externe. Une analyse en IO a été réalisée sur ce modèle afin d’évaluer la réponse corticale aux stimuli visuels et électriques. Ce travail de thèse, par des approches physiques et physiologiques complémentaires, apporte un certain nombre de réponses qui devraient permettre d’améliorer l’utilisation de futures prothèses rétiniennes par une adaptation physique des matrices d’électrodes ou des patrons de stimulations utilisées / The aim of this thesis is the functional validation of retinal implants used for vision restoration in blind patients due to the loss of photoreceptors. This work was designed to develop an animal model to experimentally validate prototypes of new implants and new stimulation protocols pattern. Firstly we used the technique of impedance spectroscopy to simulate mathematically the tissue/implant interface. These data confirm the importance of reducing the space between the stimulating electrodes and retinal tissue, as well as the importance of physical characteristics of the electrical stimulus used. In a second approach, we have compared responses of visual cortical neuronal population using optical imaging (OI), evoked either by visual or electric retinal stimulation through subretinal prosthesis. This approach has demonstrated that the stimulation of an electrode induces cortical activation that the size of the cortical response to the retinal implant stimulation is much larger than its corresponding visual stimulus. In the third part, I performed in vitro experiment to measure the performance of stimulation at the level of ganglion cells of isolated retina. We have quantified the response curve as a function of the intensity of the electrical stimulation. Finally, the thesis describes a new animal model of outter retinal degeneration. OI was also performed on this model to assess the response to the visual and retinal prosthesis stimulations. This thesis, through complementary physical and physiological approaches, provides a number of responses that can potentially improve the use of retinal prostheses through specification of their design or patterns of stimulation.