scholarly journals Epiretinal stimulation with local returns enhances selectivity at cellular resolution

2018 ◽  
Author(s):  
Victoria H. Fan ◽  
Lauren E. Grosberg ◽  
Sasidhar S. Madugula ◽  
Pawel Hottowy ◽  
Wladyslaw Dabrowski ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Electrode Array ◽  
Artificial Vision ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Cellular Resolution ◽  
Electrode Recording ◽  
Current Spread ◽  
Evoked Activity

AbstractObjectiveEpiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, potentially limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause undesirable current spread. Here, the ability of local return stimulation to improve the selective activation of RGCs at cellular resolution was evaluated.ApproachA custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation near the RGC soma with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes.Main resultsLocal return stimulation enhanced the capability to activate cells near the central electrode (<30 μm) while avoiding cells farther away (>30 μm). This resulted in an improved ability to selectively activate ON and OFF cells, including cells encoding immediately adjacent regions in the visual field.SignificanceThese results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision.Novelty & SignificanceThe effectiveness of local return stimulation for enhancing the electrical activation of retinal neurons was tested using high-density multi-electrode recording and stimulation in isolated macaque retina. The results suggest that local returns may reduce unwanted evoked activity and thus optimize the selectivity of stimulation at cellular resolution. Similar patterns could be implemented in a future high-resolution prosthesis to permit a more faithful replication of normal retinal activity for the treatment of incurable blindness.

scholarly journals Model-Based Recommendations for Optimal Surgical Placement of Epiretinal Implants

2019 ◽  
Author(s):  
Michael Beyeler ◽  
Geoffrey M. Boynton ◽  
Ione Fine ◽  
Ariel Rokem
Keyword(s):  
Visual Experience ◽  
Ganglion Cells ◽  
Electrode Array ◽  
Patient Specific ◽  
Retinal Ganglion ◽  
Retinal Implant ◽  
Implant Placement ◽  
Retinal Implants ◽  
Visual Percept

AbstractA major limitation of current electronic retinal implants is that in addition to stimulating the intended retinal ganglion cells, they also stimulate passing axon fibers, producing perceptual ‘streaks’ that limit the quality of the generated visual experience. Recent evidence suggests a dependence between the shape of the elicited visual percept and the retinal location of the stimulating electrode. However, this knowledge has yet to be incorporated into the surgical placement of retinal implants. Here we systematically explored the space of possible implant configurations to make recommendations for optimal intraocular positioning of the electrode array. Using a psychophysically validated computational model, we demonstrate that better implant placement has the potential to reduce the spatial extent of axonal activation in existing implant users by up to ∼55 %. Importantly, the best implant location, as inferred from a population of simulated virtual patients, is both surgically feasible and is relatively stable across individuals. This study is a first step towards the use of computer simulations in patient-specific planning of retinal implant surgery.

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

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Naïg Aurelia Ludmilla Chenais ◽  
Marta Jole Ildelfonsa Airaghi Leccardi ◽  
Diego Ghezzi
Keyword(s):  
High Resolution ◽  
Ganglion Cells ◽  
Artificial Vision ◽  
Wide Field ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Retinal Prostheses ◽  
Retinal Stimulation ◽  
Single Pixel ◽  
Pixel Pitch

AbstractRetinal 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.

scholarly journals Spatially Patterned Bi-electrode Epiretinal Stimulation for Axon Avoidance at Cellular Resolution

2021 ◽  
Author(s):  
Ramandeep S Vilkhu ◽  
Sasidhar S Madugula ◽  
Lauren E Grosberg ◽  
Alex R Gogliettino ◽  
Pawel Hottowy ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Ex Vivo ◽  
Single Cells ◽  
Electrode Array ◽  
Theoretical Work ◽  
Visual Signals ◽  
Artificial Vision ◽  
Cellular Resolution ◽  
Single Spike ◽  
Electrode Stimulation

Objective: Epiretinal prostheses are designed to restore vision to people blinded by photoreceptor degenerative diseases by stimulating surviving retinal ganglion cells (RGCs), which carry visual signals to the brain. However, inadvertent stimulation of RGCs at their axons can result in non-focal visual percepts, limiting the quality of artificial vision. Theoretical work has suggested that axon activation can be avoided with current stimulation designed to minimize the second spatial derivative of the induced extracellular voltage along the axon. However, this approach has not been verified experimentally at the resolution of single cells. Approach: In this work, a custom multi-electrode array (512 electrodes, 10 μm diameter, 60 μm pitch) was used to stimulate and record RGCs in macaque retina ex vivo at single-cell, single-spike resolution. RGC activation thresholds resulting from bi-electrode stimulation, which consisted of bipolar currents simultaneously delivered through two electrodes straddling an axon, were compared to activation thresholds from traditional single-electrode stimulation. Results: Across three retinal preparations, the bi-electrode stimulation strategy reduced somatic activation thresholds while increasing axonal activation thresholds, thus favoring selective somatic activation. Furthermore, individual examples revealed rescued selective activation of somas that was not possible with any individual electrode. Significance: This work suggests that a bi-electrode epiretinal stimulation strategy can reduce inadvertent axonal activation at cellular resolution, for high-fidelity artificial vision.

Image Sharpness and Contrast Tuning in the Early Visual Pathway

2017 ◽  
Vol 27 (08) ◽  
pp. 1750045 ◽  
Author(s):  
Eduardo Sánchez ◽  
Rubén Ferreiroa ◽  
Adrián Arias ◽  
Luis M. Martínez
Keyword(s):  
Functional Organization ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Local Contrast ◽  
Retinal Ganglion ◽  
Image Sharpness ◽  
Image Processing Techniques ◽  
Thalamic Relay ◽  
Processing Techniques

The center–surround organization of the receptive fields (RFs) of retinal ganglion cells highlights the presence of local contrast in visual stimuli. As RF of thalamic relay cells follow the same basic functional organization, it is often assumed that they contribute very little to alter the retinal output. However, in many species, thalamic relay cells largely outnumber their retinal inputs, which diverge to contact simultaneously several units at thalamic level. This gain in cell population as well as retinothalamic convergence opens the door to question how information about contrast is transformed at the thalamic stage. Here, we address this question using a realistic dynamic model of the retinothalamic circuit. Our results show that different components of the thalamic RF might implement filters that are analogous to two types of well-known image processing techniques to preserve the quality of a higher resolution version of the image on its way to the primary visual cortex.

scholarly journals Architecture of retinal projections to the central circadian pacemaker

2016 ◽  
Vol 113 (21) ◽  
pp. 6047-6052 ◽  
Author(s):  
Diego Carlos Fernandez ◽  
Yi-Ting Chang ◽  
Samer Hattar ◽  
Shih-Kuo Chen
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Microscopic Analysis ◽  
Brain Regions ◽  
Retinal Ganglion ◽  
Circadian Pacemaker ◽  
Retinal Neurons ◽  
Retinal Input ◽  
Innervation Patterns ◽  
Left And Right

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.

scholarly journals Radial migration: Retinal neurons hold on for the ride

2016 ◽  
Vol 215 (2) ◽  
pp. 147-149 ◽  
Author(s):  
Jeremy N. Kay
Keyword(s):  
Nervous System ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Newborn Neuron ◽  
Radial Migration ◽  
Biological Basis ◽  
Cell Biol

Newborn neuron radial migration is a key force shaping the nervous system. In this issue, Icha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201604095) use zebrafish retinal ganglion cells as a model to investigate the cell biological basis of radial migration and the consequences for retinal histogenesis when migration is impaired.

scholarly journals Transcriptional logic of cell fate specification and axon guidance in early born retinal neurons revealed by single-cell mRNA profiling

2018 ◽  
Author(s):  
Quentin Lo Giudice ◽  
Marion Leleu ◽  
Pierre J. Fabre
Keyword(s):  
Axon Guidance ◽  
Cell Fate ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Retinal Ganglion ◽  
Cell Fate Specification ◽  
Retinal Neurons ◽  
Fate Specification ◽  
Guidance Cues ◽  
Insight Into

ABSTRACTRetinal ganglion cells (RGC), together with cone photoreceptors, horizontal cells (HC) and amacrine cells (AC), are the first classes of neurons produced in the retina. Here we have profiled 5348 single retinal cells and provided a comprehensive transcriptomic atlas showing the broad diversity of the developing retina at the time when the four early-born cells are being produced. Our results show the transcriptional sequences that establish the hierarchical ordering of early cell fate specification in the retina. RGC maturation follows six waves of gene expression, giving new insight into the regulatory logic of RGC differentiation. Early-generated RGCs transcribe an increasing amount of guidance cues for young peripheral RGC axons that express the matching receptors. Finally, spatial signatures in sub-populations of RGCs allowed to define novel molecular markers that are spatially restricted during the development of the retina. Altogether this study is a valuable resource that identifies new players in mouse retinal development, shedding light on transcription factors sequence and guidance cues dynamics in space and time.

scholarly journals Light-evoked activity and BDNF regulate mitochondrial dynamics and mitochondrial localized translation

2018 ◽  
Author(s):  
Alex Kreymerman ◽  
Jessica E. Weinstein ◽  
Sahil H. Shah ◽  
David N. Buickians ◽  
Anne Faust ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Mitochondrial Dynamics ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Axon Development ◽  
Size Number ◽  
Gene And Protein Expression ◽  
Eye Opening ◽  
Evoked Activity

AbstractMitochondria coordinate diverse functions within neurites, including signaling events for axonal maintenance, and degeneration. However, less is known about the role of mitochondria in axon development and maturation. Here we find that in maturing retinal ganglion cells (RGCs) in vivo, axonal mitochondria increase in size, number, and total area throughout development. We demonstrate through multiple approaches in vivo that the mechanism underlying these mitochondrial changes are dependent on eye opening and associated neuronal activity, which can be mimicked by brain derived neurotrophic factor (BDNF). We report downstream gene and protein expression changes consistent with mitochondrial biogenesis and energetics pathways, and present evidence that the associated transcripts are localized and translated at mitochondria within axons in an activity-dependent manner. Together these data support a novel model for mitochondrial-localized translation in support of intra-axonal mitochondrial dynamics and axonal maturation.

scholarly journals Naturalistic spatiotemporal stimulus modulation during epiretinal stimulation increases the persistence of retinal ganglion cell responsivity

2020 ◽  
Author(s):  
Naïg Aurélia Ludmilla Chenais ◽  
Marta Jole Ildelfonsa Airaghi Leccardi ◽  
Diego Ghezzi
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Artificial Vision ◽  
Retinal Ganglion ◽  
Electric Pulses ◽  
Retinal Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulus Modulation ◽  
Stimulation Of ◽  
Blind Patients

AbstractObjectiveRetinal stimulation in blind patients evokes the sensation of discrete points of light called phosphenes, which allows them performing visual 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 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.ApproachA 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 resultsThe results showed that the spatial and temporal modulation of the network-mediated epiretinal stimulation prolonged the responsivity of retinal ganglion cells from 400 ms up to 4.2 s.SignificanceA 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.

scholarly journals Current Medical Therapy and Future Trends in the Management of Glaucoma Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Barbara Cvenkel ◽  
Miriam Kolko
Keyword(s):  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Future Trends ◽  
Neuroprotective Agents ◽  
Sustained Drug Delivery ◽  
Progressive Loss ◽  
Neuroprotective Therapy ◽  
Rate Of Progression ◽  
New Treatment

Glaucoma is a neurodegenerative disease characterized by progressive loss of retinal ganglion cells and their axons. Lowering of intraocular pressure (IOP) is currently the only proven treatment strategy for glaucoma. However, some patients show progressive loss of visual field and quality of life despite controlled IOP which indicates that other factors are implicated in glaucoma. Therefore, approaches that could prevent or decrease the rate of progression and do not rely on IOP lowering have gained much attention. Effective neuroprotection has been reported in animal models of glaucoma, but till now, no neuroprotective agents have been clinically approved. The present update provides an overview of currently available IOP-lowering medications. Moreover, potential new treatment targets for IOP-lowering and neuroprotective therapy are discussed. Finally, future trends in glaucoma therapy are addressed, including sustained drug delivery systems and progress toward personalized medicine.

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