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 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.

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 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.

scholarly journals Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Carolina P. B. Gracitelli ◽  
Gloria Liliana Duque-Chica ◽  
Ana Laura de Araújo Moura ◽  
Marina Roizenblatt ◽  
Balazs V. Nagy ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Retinal Ganglion Cells ◽  
Daytime Sleepiness ◽  
Epworth Sleepiness Scale ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Pupillary Reflex

Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.

scholarly journals Medical Management of Glaucoma in the 21st Century from a Canadian Perspective

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Paul Harasymowycz ◽  
Catherine Birt ◽  
Patrick Gooi ◽  
Lisa Heckler ◽  
Cindy Hutnik ◽  
...  
Keyword(s):  
Medical Management ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Field Testing ◽  
Retinal Nerve Fibre Layer ◽  
Retinal Ganglion ◽  
Canadian Perspective ◽  
Recent Developments ◽  
Nerve Fibre Layer

Glaucoma is a medical term describing a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and retinal nerve fibre layer and resulting in changes in the optic nerve head. Glaucoma is a leading cause of irreversible vision loss worldwide. With the aging population it is expected that the prevalence of glaucoma will continue to increase. Despite recent advances in imaging and visual field testing techniques that allow establishment of earlier diagnosis and treatment initiation, significant numbers of glaucoma patients are undiagnosed and present late in the course of their disease. This can lead to irreversible vision loss, reduced quality of life, and a higher socioeconomic burden. Selection of therapeutic approaches for glaucoma should be based on careful ocular examination, patient medical history, presence of comorbidities, and awareness of concomitant systemic therapies. Therapy should also be individualized to patients’ needs and preferences. Recent developments in this therapeutic field require revisiting treatment algorithms and integration of traditional and novel approaches in order to ensure optimal visual outcomes. This article provides an overview of recent developments and practice trends in the medical management of glaucoma in Canada. A discussion of the surgical management is beyond the scope of this paper.

Selectivity for Multiple Stimulus Features in Retinal Ganglion Cells

2006 ◽  
Vol 96 (5) ◽  
pp. 2724-2738 ◽  
Author(s):  
Adrienne L. Fairhall ◽  
C. Andrew Burlingame ◽  
Ramesh Narasimhan ◽  
Robert A. Harris ◽  
Jason L. Puchalla ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Electrode Array ◽  
Retinal Ganglion ◽  
Temporal Features ◽  
Multiple Stimulus ◽  
Feature Selectivity ◽  
Small Set ◽  
Stimulus Features

Under normal viewing conditions, retinal ganglion cells transmit to the brain an encoded version of the visual world. The retina parcels the visual scene into an array of spatiotemporal features, and each ganglion cell conveys information about a small set of these features. We study the temporal features represented by salamander retinal ganglion cells by stimulating with dynamic spatially uniform flicker and recording responses using a multi-electrode array. While standard reverse correlation methods determine a single stimulus feature—the spike-triggered average—multiple features can be relevant to spike generation. We apply covariance analysis to determine the set of features to which each ganglion cell is sensitive. Using this approach, we found that salamander ganglion cells represent a rich vocabulary of different features of a temporally modulated visual stimulus. Individual ganglion cells were sensitive to at least two and sometimes as many as six features in the stimulus. While a fraction of the cells can be described by a filter-and-fire cascade model, many cells have feature selectivity that has not previously been reported. These reverse models were able to account for 80–100% of the information encoded by ganglion cells.

scholarly journals Retinal waves but not visual experience are required for development of retinal direction selectivity maps

2021 ◽  
Author(s):  
Alexandre Tiriac ◽  
Karina Bistrong ◽  
Marla Feller
Keyword(s):  
Calcium Imaging ◽  
Visual Experience ◽  
Ganglion Cells ◽  
Vertical Component ◽  
Direction Selectivity ◽  
The Body ◽  
Retinal Ganglion ◽  
Retinal Waves ◽  
Two Photon ◽  
Eye Opening

Retinal waves and visual experience have been implicated in the formation of retinotopic and eye-specific maps throughout the visual system, but whether either play a role in the development of the maps within the retina itself is unknown. We explore this question using direction-selective retinal ganglion cells, which are organized into a map that aligns to the body and gravitational axes of optic flow. Using two-photon population calcium imaging, we find that the direction selectivity map is present at eye opening and is unaltered by dark-rearing. Remarkably, the horizontal component of the direction selectivity map is absent in mice lacking normal retinal waves, whereas the vertical component remains normal. These results indicate that intrinsic patterns of activity, rather than extrinsic motion signals are critical for the establishment of direction selectivity maps in the retina.

scholarly journals Glutamate Stimulation Dysregulates AMPA Receptors-Induced Signal Transduction Pathway in Leber’s Inherited Optic Neuropathy Patient-Specific hiPSC-Derived Retinal Ganglion Cells

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 625
Author(s):  
Yang ◽  
Nguyen ◽  
Lin ◽  
Yarmishyn ◽  
Chen ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Neuropathy ◽  
Ampa Receptors ◽  
Ganglion Cells ◽  
Genetic Disorder ◽  
Signal Transduction Pathway ◽  
Cellular Level ◽  
Scaffold Proteins ◽  
Patient Specific ◽  
Retinal Ganglion

The mitochondrial genetic disorder, Leber’s hereditary optic neuropathy (LHON), is caused by a mutation in MT-ND4 gene, encoding NADH dehydrogenase subunit 4. It leads to the progressive death of retinal ganglion cells (RGCs) and causes visual impairment or even blindness. However, the precise mechanisms of LHON disease penetrance and progression are not completely elucidated. Human-induced pluripotent stem cells (hiPSCs) offer unique opportunities to investigate disease-relevant phenotypes and regulatory mechanisms underlying LHON pathogenesis at the cellular level. In this study, we successfully generated RGCs by differentiation of LHON patient-specific hiPSCs. We modified the protocol of differentiation to obtain a more enriched population of single-cell RGCs for LHON study. Based on assessing morphology, expression of specific markers and electrophysiological activity, we found that LHON-specific hiPSC-derived were more defective in comparison with normal wild-type RGCs. Based on our previous study, whereby by using microarray analysis we identified that the components of glutamatergic synapse signaling pathway were significantly downregulated in LHON-specific RGCs, we focused our study on glutamate-associated α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. We found that the protein expression levels of the subunits of the AMPA receptor, GluR1 and GluR2, and their associated scaffold proteins were decreased in LHON-RGCs. By performing the co-immunoprecipitation assay, we found several differences in the efficiencies of interaction between AMPA subunits and scaffold proteins between normal and LHON-specific RGCs.

Emergence of complex receptive field properties of ganglion cells in the developing turtle retina

1995 ◽  
Vol 73 (4) ◽  
pp. 1355-1364 ◽  
Author(s):  
E. Sernagor ◽  
N. M. Grzywacz
Keyword(s):  
Receptive Field ◽  
Retinal Ganglion Cells ◽  
Visual Experience ◽  
Ganglion Cells ◽  
Directional Selectivity ◽  
Retinal Ganglion ◽  
Synaptic Connections ◽  
Embryonic Cells ◽  
Receptive Field Properties ◽  
Spatiotemporal Receptive Field

1. Receptive field properties of adult retinal ganglion cells are well documented, but little is known about their development. We made extracellular recordings of activity from turtle retinal ganglion cells during embryogenesis (stages 22-26), during the first 40 days posthatching, and in adults. 2. From stage 22 the cells fired in spontaneous recurring bursts, and from stage 23 they responded to light. Polar plots of the responses to motion were highly anisotropic in early embryonic cells. More than 40% of embryonic cells exhibited multiaxis anisotropy, and only 6% were statistically isotropic. The incidence of anisotropic cells gradually decreased throughout development. The incidence of isotropic cells and the excitatory receptive field diameters of all ganglion cells gradually increased during development and their maturation coincided with the disappearance of the spontaneous bursts (2-4 wk posthatching). 3. Both sensitivities to stimulus orientation and direction of motion were observed at the earliest stages of development. However, orientation selectivity reached a peak incidence at hatching, whereas directional selectivity completely disappeared, only to reappear in adults. 4. These results show that mature spatiotemporal receptive field properties of retinal ganglion cells emerge from initially highly anisotropic properties, which may reflect an immature, polarized dendritic layout. Their maturation might be mediated by dendritic outgrowth and strengthening of excitatory synaptic connections, which could be induced by spontaneous activity and driven to maturation by exposure to light at birth. Mature directional selectivity seems to require visual experience or the late establishment of a specialized inhibitory synaptic drive.

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