Multi-channel transorbital electrical stimulation for effective stimulation of posterior retina.
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ABSTRACT:
SUBMITTER: Lee S
PROVIDER: S-EPMC8105361 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Retinal prostheses have shown some clinical success in patients with retinitis pigmentosa and age-related macular degeneration. However, even after the implantation of a retinal prosthesis, the patient's visual acuity is at best less than 20/420. Reduced visual acuity may be explained by a decrease in the signal-to-noise ratio due to the spontaneous hyperactivity of retinal ganglion cells (RGCs) found in degenerate retinas. Unfortunately, abnormal retinal rewiring, commonly observed in degenerate retinas, has rarely been considered for the development of retinal prostheses. The purpose of this study was to investigate the aberrant retinal network response to electrical stimulation in terms of the spatial distribution of the electrically evoked RGC population. An 8 × 8 multielectrode array was used to measure the spiking activity of the RGC population. RGC spikes were recorded in wild-type [C57BL/6J; P56 (postnatal day 56)], rd1 (P56), rd10 (P14 and P56) mice, and macaque [wild-type and drug-induced retinal degeneration (RD) model] retinas. First, we performed a spike correlation analysis between RGCs to determine RGC connectivity. No correlation was observed between RGCs in the control group, including wild-type mice, rd10 P14 mice, and wild-type macaque retinas. In contrast, for the RD group, including rd1, rd10 P56, and RD macaque retinas, RGCs, up to approximately 400-600 μm apart, were significantly correlated. Moreover, to investigate the RGC population response to electrical stimulation, the number of electrically evoked RGC spikes was measured as a function of the distance between the stimulation and recording electrodes. With an increase in the interelectrode distance, the number of electrically evoked RGC spikes decreased exponentially in the control group. In contrast, electrically evoked RGC spikes were observed throughout the retina in the RD group, regardless of the inter-electrode distance. Taken together, in the degenerate retina, a more strongly coupled retinal network resulted in the widespread distribution of electrically evoked RGC spikes. This finding could explain the low-resolution vision in prosthesis-implanted patients.
| S-EPMC9114441 | biostudies-literature
Project description:Electrical brain stimulation (EBS) is an appealing method to treat neurological disorders. To achieve optimal stimulation effects and a better understanding of the underlying brain mechanisms, neuroscientists have proposed computational modeling studies for a decade. Recently, multi-scale models that combine a volume conductor head model and multi-compartmental models of cortical neurons have been developed to predict stimulation effects on the macroscopic and microscopic levels more precisely. As the need for better computational models continues to increase, we overview here recent multi-scale modeling studies; we focused on approaches that coupled a simplified or high-resolution volume conductor head model and multi-compartmental models of cortical neurons, and constructed realistic fiber models using diffusion tensor imaging (DTI). Further implications for achieving better precision in estimating cellular responses are discussed.
| S-EPMC5662877 | biostudies-literature
Project description:The search for therapeutic strategies to promote neuronal regeneration following injuries toward functional recovery is of great importance. Brief low-frequency electrical stimulation (ES) has been reported as a useful method to improve neuronal regeneration in different animal models; however, the effect of ES on single neuron behavior has not been shown. Here, we study the effect of brief ES on neuronal regeneration of the CNS of adult medicinal leeches. Studying the regeneration of selected sets of identified neurons allow us to quantify the ES effect per cell type at the single-cell level. Chains of the CNS that were subjected to cut injury were observed for 3?d, and the spontaneous regeneration was compared with the electrically stimulated injured chains. We show that the ES improves the efficiency of regeneration of Retzius cells, as larger masses of the total branching tree traverse the injury site with better directed growth with no effect on the average branching tree length. No antero-posterior polarity was found along regeneration within the leech CNS. Moreover, the microglial cell distribution was examined revealing more microglial cells in proximity to the stimulation site compared with non-stimulated. Our results lay a foundation for future ES-based neuroregenerative therapies.
| S-EPMC7317182 | biostudies-literature
Project description:Epiretinal implants for the blind are designed to stimulate surviving retinal neurons, thus bypassing the diseased photoreceptor layer. Single-unit or multielectrode recordings from isolated animal retina are commonly used to inform the design of these implants. However, such electrical recordings provide limited information about the spatial patterns of retinal activation. Calcium imaging overcomes this limitation, as imaging enables high spatial resolution mapping of retinal ganglion cell (RGC) activity as well as simultaneous recording from hundreds of RGCs. Prior experiments in amphibian retina have demonstrated proof of principle, yet experiments in mammalian retina have been hindered by the inability to load calcium indicators into mature mammalian RGCs. Here, we report a method for labeling the majority of ganglion cells in adult rat retina with genetically encoded calcium indicators, specifically GCaMP3 and GCaMP5G. Intravitreal injection of an adeno-associated viral vector targets ∼85% of ganglion cells with high specificity. Because of the large fluorescence signals provided by the GCaMP sensors, we can now for the first time visualize the response of the retina to electrical stimulation in real-time. Imaging transduced retinas mounted on multielectrode arrays reveals how stimulus pulse shape can dramatically affect the spatial extent of RGC activation, which has clear implications in prosthetic applications. Our method can be easily adapted to work with other fluorescent indicator proteins in both wild-type and transgenic mammals.
| S-EPMC3628009 | biostudies-literature
Project description:Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual information, is a potentially better alternative to electrical stimulation widely used in current retinal prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no subretinal electrical or chemical stimulation study has stimulated the OFF and ON pathways differentially through inner retinal activation. Here, we demonstrate the feasibility of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way. We show that controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way for future development of a neurotransmitter-based subretinal prosthesis offering more naturalistic vision and better visual acuity than electrical prostheses.
| S-EPMC5144088 | biostudies-other
Project description:Direct current (DC) electrical stimulation has been shown to have remarkable effects on regulating cell behaviors. Translation of this technology to clinical uses, however, has to overcome several obstacles, including Joule heat production, changes in pH and ion concentration, and electrode products that are detrimental to cells. Application of DC voltages in thick tissues where their thickness is >0.8 mm caused significant changes in temperature, pH, and ion concentrations. In this study, we developed a multifield and -chamber electrotaxis chip, and various stimulation schemes to determine effective and safe stimulation strategies to guide the migration of human vascular endothelial cells. The electrotaxis chip with a chamber thickness of 1 mm allows 10 voltages applied in one experiment. DC electric fields caused detrimental effects on cells in a 1 mm chamber that mimicking 3D tissue with a decrease in cell migration speed and an increase in necrosis and apoptosis. Using the chip, we were able to select optimal stimulation schemes that were effective in guiding cells with minimal detrimental effects. This experimental system can be used to determine optimal electrical stimulation schemes for cell migration, survival with minimal detrimental effects on cells, which will facilitate to bring electrical stimulation for in vivo use.
| S-EPMC8370347 | biostudies-literature
Project description:Purpose: To investigate the effect of transcorneal electrical stimulation (TES) on the retina of wildtype Brown Norway (BN) rats by gene expression profiling. Methods: TES was applied to BN adult wildtype rat retina in vivo for 1h (1ms biphasic pulses at 20Hz; current: 200 M-BM-5A). RNA was isolated, processed and used for microarray-based expression profiling 4hrs after initial TES. An expression profile was generated for genes differentially expressed at 4hrs after TES vs. sham stimulated animals using a fold change cutoff of 1.2. We validated the profile by real-time quantitative reverse transcription-polymerase chain reaction (qPCR). In addition, the application of TES was verified at the structural and functional level. Results: Transcriptome changes associated with TES vs. sham stimulated BN wildtype retina were identified. 490 genes were differentially expressed in TES and included well-known genes as well as a large number of novel genes. Electrophysiological recordings showed physiological retinal function after TES and structural in vivo and ex vivo studies revealed intact retinal layers. Conclusion: Our results demonstrate that TES applied to the retina of wildtype BN rats induce a variety of transcriptome level changes and may help to understand the mechanisms underlying TES. In addition TES has no negative effect on structure and function of wildtype BN retina 24hrs after application. RNA isolation and Microarray studies 4 animals were euthanized 4h after TES or respective sham treatment. Extraction of total RNA was performed using the RNeasy Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. QIAshredder mini-spin columns (Qiagen) as well as needle and syringe homogenization were applied for tissue homogenization. To ensure proper integrity all RNA used in our experiments showed single peaks for the 18S and 28S bands as determined by the Agilent 2100 Bioanalyzer using the RNA 6000 Nano LabChip Kit (both Agilent Technologies Inc., CA, USA) following the manufacturer's instructions. The purity and concentration of total RNA was determined by absorbance measurements at 260 and 280nm using a Nanodrop ND-1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE, USA). All RNA that did not have a 260/280 ratio between 1.9 and 2.1 was discarded to ensure high quality of samples. Respective RNAs from stimulated and sham samples were used to generate double-stranded cDNA with the T7-oligo (dT) primer according to GeneChipM-BM-. (Affymetrix Inc., Santa Clara, CA, USA) two cycle target labeling protocol as described by the manufacturer. The processed cDNA was hybridized to Affymetrix GeneChipM-BM-. Rat Gene 1.0 ST arrays for 18M-bM-^@M-^S24h (Affymetrix Inc.). Four TES and four sham replicates were used for hybridization to Microarray GeneChipsM-BM-.. Each microarray was washed and stained with streptavidinM-bM-^@M-^Sphycoerythrin and scanned at a 6M-NM-<m resolution with Agilent Technologies model G2500A GeneArray scanner. A visual quality control measurement was performed to ensure proper hybridization after each chip was scanned. Additional quality control parameters such as scaling factors used to normalize the chips, average background, and noise were also evaluated. Microarray analysis For statistical analysis of microarray data all cell files were imported to GeneSpring GX software (Agilent Technologies Inc.) where GC-RMA algorithm was applied to yield log signal values on each probe set. All transcripts with a minimum change of 1.2 fold together with a p value less than 0.05 were selected using Significance Analysis of Microarray (SAM) (Tusher VG, 2001). The visualization of the relationships between the samples by principal component analysis (PCA) based on the GC-RMA signal and hierarchical clustering using the Pearson correlation was obtained using PARTEK Genomics Suite version 6.4. All differentially regulated genes were imported into Ingenuity Pathway Analysis (Ingenuity Systems, CA, USA) for generation of networks and canonical pathway analysis. The data set containing all significant gene identifiers along with corresponding expression and significance values was uploaded into the application. Each identifier was mapped to its corresponding object in Ingenuity's Knowledge Base. The set fold change cutoff identified all molecules whose expression was significantly differentially regulated. These network eligible molecules were overlaid onto a global molecular network developed from information contained in IngenuityM-bM-^@M-^Ys Knowledge Base. Networks were then algorithmically generated based on their connectivity. The functional analysis of a network identified the biological functions using a right-tailed FisherM-bM-^@M-^Ys exact test that were most significant to the molecules in the network. Canonical pathways analysis identified the pathways from the Ingenuity Pathways Analysis library of canonical pathways that were most significant to the data set. The significance of the association between the data set and the canonical pathway was measured in 2 ways: 1) A ratio of the number of molecules from the data set that map to the pathway divided by the total number of molecules that map to the canonical pathway is displayed. 2) FisherM-bM-^@M-^Ys exact test was used to calculate a p-value determining the probability that the association between the genes in the dataset and the canonical pathway is explained by chance alone.
2011-11-21 | E-GEOD-26174 | biostudies-arrayexpress
Project description:Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.
| S-EPMC6917705 | biostudies-literature
Project description:Retinal implants are used to replace lost photoreceptors in blind patients suffering from retinopathies such as retinitis pigmentosa. Patients wearing implants regain some rudimentary visual function. However, it is severely limited compared to normal vision because non-physiological stimulation strategies fail to selectively activate different retinal pathways at sufficient spatial and temporal resolution. The development of improved stimulation strategies is rendered difficult by the large space of potential stimuli. Here we systematically explore a subspace of potential stimuli by electrically stimulating healthy and blind mouse retina in epiretinal configuration using smooth Gaussian white noise delivered by a high-density CMOS-based microelectrode array. We identify linear filters of retinal ganglion cells (RGCs) by fitting a linear-nonlinear-Poisson (LNP) model. Our stimulus evokes spatially and temporally confined spiking responses in RGC which are accurately predicted by the LNP model. Furthermore, we find diverse shapes of linear filters in the linear stage of the model, suggesting diverse preferred electrical stimuli of RGCs. The linear filter base identified by our approach could provide a starting point of a model-guided search for improved stimuli for retinal prosthetics.
| S-EPMC7090015 | biostudies-literature
Project description:Hair loss, a common and distressing symptom, has been plaguing humans. Various pharmacological and nonpharmacological treatments have been widely studied to achieve the desired effect for hair regeneration. As a nonpharmacological physical approach, physiologically appropriate alternating electric field plays a key role in the field of regenerative tissue engineering. Here, a universal motion-activated and wearable electric stimulation device that can effectively promote hair regeneration via random body motions was designed. Significantly facilitated hair regeneration results were obtained from Sprague-Dawley rats and nude mice. Higher hair follicle density and longer hair shaft length were observed on Sprague-Dawley rats when the device was employed compared to conventional pharmacological treatments. The device can also improve the secretion of vascular endothelial growth factor and keratinocyte growth factor and thereby alleviate hair keratin disorder, increase the number of hair follicles, and promote hair regeneration on genetically defective nude mice. This work provides an effective hair regeneration strategy in the context of a nonpharmacological self-powered wearable electronic device.
| S-EPMC6881522 | biostudies-literature