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      Photovoltaic restoration of sight with high visual acuity

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          Abstract

          Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We demonstrate that subretinal arrays with 70 μm photovoltaic pixels provide highly localized stimulation, with electrical and visual receptive fields of comparable sizes in rat retinal ganglion cells. Similarly to normal vision, retinal response to prosthetic stimulation exhibits flicker fusion at high frequencies, adaptation to static images and non-linear spatial summation. In rats with retinal degeneration, these photovoltaic arrays provide spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in pigmented rats. Ease of implantation of these wireless and modular arrays, combined with their high resolution opens the door to functional restoration of sight.

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          Most cited references53

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          Spatio-temporal correlations and visual signalling in a complete neuronal population.

          Statistical dependencies in the responses of sensory neurons govern both the amount of stimulus information conveyed and the means by which downstream neurons can extract it. Although a variety of measurements indicate the existence of such dependencies, their origin and importance for neural coding are poorly understood. Here we analyse the functional significance of correlated firing in a complete population of macaque parasol retinal ganglion cells using a model of multi-neuron spike responses. The model, with parameters fit directly to physiological data, simultaneously captures both the stimulus dependence and detailed spatio-temporal correlations in population responses, and provides two insights into the structure of the neural code. First, neural encoding at the population level is less noisy than one would expect from the variability of individual neurons: spike times are more precise, and can be predicted more accurately when the spiking of neighbouring neurons is taken into account. Second, correlations provide additional sensory information: optimal, model-based decoding that exploits the response correlation structure extracts 20% more information about the visual scene than decoding under the assumption of independence, and preserves 40% more visual information than optimal linear decoding. This model-based approach reveals the role of correlated activity in the retinal coding of visual stimuli, and provides a general framework for understanding the importance of correlated activity in populations of neurons.
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            Parallel processing in the mammalian retina.

            Our eyes send different 'images' of the outside world to the brain - an image of contours (line drawing), a colour image (watercolour painting) or an image of moving objects (movie). This is commonly referred to as parallel processing, and starts as early as the first synapse of the retina, the cone pedicle. Here, the molecular composition of the transmitter receptors of the postsynaptic neurons defines which images are transferred to the inner retina. Within the second synaptic layer - the inner plexiform layer - circuits that involve complex inhibitory and excitatory interactions represent filters that select 'what the eye tells the brain'.
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              The contrast sensitivity of retinal ganglion cells of the cat.

              1. Spatial summation within cat retinal receptive fields was studied by recording from optic-tract fibres the responses of ganglion cells to grating patterns whose luminance perpendicular to the bars varied sinusoidally about the mean level. 2. Summation over the receptive fields of some cells (X-cells) was found to be approximately linear, while for other cells (Y-cells) summation was very non-linear. 3. The mean discharge frequency of Y-cells (unlike that of X-cells) was greatly increased when grating patterns drifted across their receptive fields. 4. In twenty-one X-cells the relation between the contrast and spatial frequency of drifting sinusoidal gratings which evoked the same small response was measured. In every case it was found that the reciprocal of this relation, the contrast sensitivity function, could be satisfactorily described by the difference of two Gaussian functions. 5. This finding supports the hypothesis that the sensitivities of the antagonistic centre and surround summating regions of ganglion cell receptive fields fall off as Gaussian functions of the distance from the field centre. 6. The way in which the sensitivity of an X-cell for a contrast-edge pattern varied with the distance of the edge from the receptive field centre was determined and found to be consistent with the cell's measured contrast sensitivity function. 7. Reducing the retinal illumination produced changes in the contrast sensitivity function of an X-cell which suggested that the diameters of the summating regions of the receptive field increased while the surround region became relatively ineffective.
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                Author and article information

                Journal
                9502015
                8791
                Nat Med
                Nat. Med.
                Nature medicine
                1078-8956
                1546-170X
                1 April 2015
                27 April 2015
                May 2015
                01 November 2015
                : 21
                : 5
                : 476-482
                Affiliations
                [1 ]Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA, USA
                [2 ]Department of Ophthalmology, Stanford University, Stanford, CA, USA
                [3 ]Inserm UMR_S968, Institut de la Vision, Paris, France
                [4 ]Department of Electrical Engineering, Stanford University, Stanford, CA, USA
                [5 ]Santa Cruz Institute for Particle Physics, University of California Santa Cruz, Santa Cruz, CA, USA
                [6 ]The Mina & Everard Goodman Faculty of Life Sciences, Bar Ilan University, Israel
                [7 ]Institute of Photonics, University of Strathclyde, Glasgow, UK
                Author notes
                [* ]Correspondence to: ggoetz@ 123456stanford.edu
                [†]

                These authors contributed equally to this work, and share primary authorship.

                [‡]

                These authors contributed equally to supervision of this work, and share senior authorship.

                Article
                NIHMS676393
                10.1038/nm.3851
                4601644
                25915832
                d32705d3-2cbb-4194-a18e-5355c0d43ac1
                History
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                Medicine
                Medicine

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