Direct Activation and Temporal Response Properties of Rabbit Retinal Ganglion Cells Following Subretinal Stimulation

2009 ◽  
Vol 102 (5) ◽  
pp. 2982-2993 ◽  
Author(s):  
David Tsai ◽  
John W. Morley ◽  
Gregg J. Suaning ◽  
Nigel H. Lovell
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Subretinal Space ◽  
High Frequency Stimulation ◽  
Retinal Ganglion ◽  
Photoreceptor Layer ◽  
Direct Activation ◽  
Frequency Stimulation ◽  
Safety Considerations

In the last decade several groups have been developing vision prostheses to restore visual perception to the profoundly blind. Despite some promising results from human trials, further understanding of the neural mechanisms involved is crucial for improving the efficacy of these devices. One of the techniques involves placing stimulating electrodes in the subretinal space between the photoreceptor layer and the pigment epithelium to evoke neural responses in the degenerative retina. This study used cell-attached and whole cell current-clamp recordings to investigate the responses of rabbit retinal ganglion cells (RGCs) following subretinal stimulation with 25-μm-diameter electrodes. We found that direct RGC responses with short latency (≤2 ms using 0.1-ms pulses) could be reliably elicited. The thresholds for these responses were reported for on, off, and on–off RGCs over pulse widths 0.1–5.0 ms. During repetitive stimulation these direct activation responses were more readily elicited than responses arising from stimulation of the retinal network. The temporal spiking characteristics of RGCs were characterized as a function of stimulus configurations. We found that the response profiles could be generalized into four classes with distinctive properties. Our results suggest that for subretinal vision prostheses short pulses are preferable for efficacy and safety considerations, and that direct activation of RGCs will be necessary for reliable activation during high-frequency stimulation.

scholarly journals Pigment epithelium-derived factor protects retinal ganglion cells

2007 ◽  
Vol 8 (1) ◽  
Author(s):  
Iok-Hou Pang ◽  
Hong Zeng ◽  
Debra L Fleenor ◽  
Abbot F Clark
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Retinal Ganglion ◽  
Pigment Epithelium Derived Factor

scholarly journals Insights from Computational Modelling: Selective Stimulation of Retinal Ganglion Cells

2020 ◽  
pp. 233-247
Author(s):  
Tianruo Guo ◽  
David Tsai ◽  
Siwei Bai ◽  
Mohit Shivdasani ◽  
Madhuvanthi Muralidharan ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Computational Models ◽  
Ganglion Cells ◽  
Computational Modelling ◽  
Retinal Ganglion ◽  
Retinal Prostheses ◽  
Differential Activation ◽  
Photoreceptor Layer ◽  
Suprachoroidal Space ◽  
Wide Range

AbstractImprovements to the efficacy of retinal neuroprostheses can be achieved by developing more sophisticated neural stimulation strategies to enable selective or differential activation of specific retinal ganglion cells (RGCs). Recent retinal studies have demonstrated the ability to differentially recruit ON and OFF RGCs – the two major information pathways of the retina – using high-frequency electrical stimulation (HFS). However, there remain many unknowns, since this is a relatively unexplored field. For example, can we achieve ON/OFF selectivity over a wide range of stimulus frequencies and amplitudes? Furthermore, existing demonstrations of HFS efficacy in retinal prostheses have been based on epiretinal placement of electrodes. Other clinically popular techniques include subretinal or suprachoroidal placement, where electrodes are located at the photoreceptor layer or in the suprachoroidal space, respectively, and these locations are quite distant from the RGC layer. Would HFS-based differential activation work from these locations? In this chapter, we conducted in silico investigations to explore the generalizability of HFS to differentially active ON and OFF RGCs. Computational models are particularly well suited for these investigations. The electric field can be accurately described by mathematical formulations, and simulated neurons can be “probed” at resolutions well beyond those achievable by today’s state-of-the-art experimental techniques.

Photovoltaic stimulation efficiently evokes network-mediated activity of retinal ganglion cells

2019 ◽  
Author(s):  
Naïg A. L. Chenais ◽  
Marta J. I. Airaghi Leccardi ◽  
Diego Ghezzi
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Biophysical Model ◽  
High Frequency Stimulation ◽  
Retinal Ganglion ◽  
Cell Coupling ◽  
Inner Retina ◽  
Stimulation Of

AbstractObjectivePhotovoltaic retinal prostheses theoretically offer the possibility of standalone high-resolution electrical stimulation of the retina. However, in artificial vision, achieving locally selective epiretinal stimulation is particularly challenging, on the grounds of axonal activation and electrical cell coupling.ApproachHere we show that electrical and photovoltaic stimulation of dystrophic retinal circuits with capacitive-like pulses leads to a greater efficiency for indirect network-mediated activation of retinal ganglion cells. In addition, a biophysical model of the inner retina stimulation is proposed to investigate the waveform and duration commitments in the genesis of indirect activity of retinal ganglion cells.Main resultsBoth in-vitro and in-silico approaches suggest that the application of long voltage pulses or gradual voltage changes are more effective to sustainably activate the inner excitatory and inhibitory layers of the retina, thus leading to a reproducible indirect response. The involvement of the inhibitory feedback from amacrine cells in the forming of indirect patterns represents a novel biological tool to locally cluster the response of the retinal ganglion cells.SignificanceThese results demonstrate that recruiting inner retina cells with epiretinal stimulation enables not only to bypass axonal stimulation but also to obtain a more focal activation thanks to the natural lateral inhibition. In this perspective, the use of capacitive-like waveforms generated by photovoltaic prostheses may allow improving the neural response resolution while standing high-frequency stimulation.

scholarly journals Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons

2020 ◽  
Vol 22 (1) ◽  
pp. 369
Author(s):  
Susanne Bürger ◽  
Jie Meng ◽  
Annette Zwanzig ◽  
Mike Beck ◽  
Maik Pankonin ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Laminin Receptor ◽  
Retinal Ganglion ◽  
Retinal Neurons ◽  
Differential Survival ◽  
Hypoxic Conditions ◽  
Pigment Epithelium Derived Factor ◽  
Inhibition Of Angiogenesis

The demise of retinal ganglion cells (RGCs) is characteristic of diseases of the retina such as glaucoma and diabetic or ischemic retinopathies. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein that mediates neuroprotection and inhibition of angiogenesis in the retina. We have studied expression and regulation of two of several receptors for PEDF, patatin-like phospholipase 2 gene product/PEDF-R and laminin receptor (LR), in serum-starved RGC under normoxia and hypoxia and investigated their involvement in the survival of retinal neuronal cells. We show that PEDF-R and LR are co-expressed in RGC and R28 retinal precursor cells. Expression of both receptors was enhanced in the presence of complex secretions from retinal glial (Müller) cells and upregulated by VEGF and under hypoxic conditions. PEDF-R- and LR-knocked-down cells demonstrated a markedly attenuated expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and neuroprotective mediators (PEDF, VEGF, BDNF) suggesting that both PEDF-R and LR mediate pro-survival effects of PEDF on RGC. While this study does not provide evidence for a differential survival-promoting influence of either PEDF-R or LR, it nevertheless highlights the importance of both PEDF receptors for the viability of retinal neurons.

scholarly journals Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

2014 ◽  
Vol 25 (2) ◽  
pp. 234-244 ◽  
Author(s):  
Chizu Nakamoto ◽  
Soh-Leh Kuan ◽  
Amy S. Findlay ◽  
Elaine Durward ◽  
Zhufeng Ouyang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Neuronal Cell ◽  
Amacrine Cells ◽  
Progression Rate ◽  
Retinal Ganglion ◽  
Displaced Amacrine Cells

For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor [EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine cells decreases. Conversely, knockdown of Nel expression by transposon-mediated introduction of RNA interference constructs results in decrease in RGC number and increase in the number of displaced amacrine cells. Modifications of Nel expression levels do not appear to affect proliferation of retinal progenitor cells, but they significantly alter the progression rate of RGC differentiation from the central retina to the periphery. Furthermore, Nel protects RGCs from apoptosis during retinal development. These results indicate that Nel positively regulates RGC production by promoting their differentiation and survival during development.

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