computational-modeling-retinal-neurons-for-visual-prosthesis-research

Computational Modeling of Retinal Neurons for Visual Prosthesis Research - Fundamental Approaches

Computational modeling has become an increasingly important method in neural engineering due to its capacity to predict behaviors of in vivo and in vitro ...

The University of Sydney

Electrical stimulation of excitable cells provides therapeutic benefits for a variety of medical conditions, including restoration of partial vision to those blinded via some types of retinal degeneration. To improve visual percepts elicited by the current technology, researchers are conducting acute electrophysiology experiments, mainly in cats. However, the rat can provide a model of a range of retinal diseases and possesses a sufficiently large eye to be used in this field. This article presents a long-term anesthetic protocol to enable electrophysiology experiments to further the development of visual prostheses. Six Long-Evans rats (aged between 14 and 16 weeks) were included in this study. Surgical anesthesia was maintained for more than 15 h by combining constant intravenous infusion of ketamine (24.0-34.5 mg/kg/h), xylazine (0.9-1.2 mg/kg/h), and inhaled isoflurane in oxygen (<0.5%). Overall heart rate, respiratory rate, and body temperature remained between 187-233 beats/min, 45-58 breaths/min, and 36-38 °C, respectively. Neural responses to 200-ms light pulses were recorded from the superior colliculus using a 32-channel neural probe at the beginning and before termination of the experiment. Robust responses were recorded from distinct functional types of retinal pathways. In addition, a platinum electrode was implanted in the retrobulbar space. The retina was electrically stimulated, and the activation threshold was determined to be 5.24 ± 0.24 μC/cm . This protocol may be used not only in the field of visual prosthesis research, but in other research areas requiring longer term acute experiments.

Long-term anesthetic protocol in rats: feasibility in electrophysiology studies in visual prosthesis.

Visual prostheses, optogenetics, stem cell and gene therapies: splitting the cake.

Recent retinal studies have directed more attention to sophisticated stimulation strategies based on high-frequency (>1.0 kHz) electrical stimulation (HFS). In these studies, each retinal ganglion cell (RGC) type demonstrated a characteristic stimulus-strength-dependent response to HFS, offering the intriguing possibility of focally targeting retinal neurons to provide useful visual information by retinal prosthetics. Ionic mechanisms are known to affect the responses of electrogenic cells during electrical stimulation. However, how these mechanisms affect RGC responses is not well understood at present, particularly when applying HFS. Here, we investigate this issue via an  model of the RGC. We calibrate and validate the model using an  retinal preparation. An RGC model based on accurate biophysics and realistic representation of cell morphology, was used to investigate how RGCs respond to HFS. The model was able to closely replicate the stimulus-strength-dependent suppression of RGC action potentials observed experimentally. Our results suggest that spike inhibition during HFS is due to local membrane hyperpolarization caused by outward membrane currents near the stimulus electrode. In addition, the extent of HFS-induced inhibition can be largely altered by the intrinsic properties of the inward sodium current. Finally, stimulus-strength-dependent suppression can be modulated by a wide range of stimulation frequencies, under generalized electrode placement conditions.  experiments verified the computational modeling data. This modeling and experimental approach can be extended to further our understanding on the effects of novel stimulus strategies by simulating RGC stimulus-response profiles over a wider range of stimulation frequencies and electrode locations than have previously been explored.

Mediating Retinal Ganglion Cell Spike Rates Using High-Frequency Electrical Stimulation.

A cochlear implant (CI) implements a variety of sound processing algorithms that seek to improve speech intelligibility. Typically, only a small number of parameter combinations are evaluated with recipients but the optimal configuration may differ for individuals. The present study evaluates a novel methodology which uses the output signal to noise ratio (OSNR) to predict complete psychometric functions that relate speech recognition to signal to noise ratio for individual CI recipients.

Prediction of Individual Cochlear Implant Recipient Speech Perception With the Output Signal to Noise Ratio Metric.

Editorial: A Conversation With the Brain: Can We Speak Its Language?

Neural implants provide effective treatment and diagnosis options for diseases where pharmaceutical therapies are missing or ineffective. These active implantable medical devices (AIMDs) are designed to remain implanted and functional over decades. A key factor for achieving reliability and longevity are cleaning procedures used during manufacturing to prevent failures associated with contaminations. The Implantable Devices Group (IDG) at University College London (UCL) pioneered an approach which involved a cocktail of reagents described as "Leslie's soup". This process proved to be successful but no extensive evaluation of this method and the cocktail's ingredients have been reported so far. Our study addressed this gap by a comprehensive analysis of the efficacy of this cleaning method. Surface analysis techniques complemented adhesion strengths methods to identify residues of contaminants like welding flux, solder residues or grease during typical assembly processes. Quantitative data prove the suitability of "Leslie's soup" for cleaning of ceramic components during active implant assembly when residual ionic contaminations were removed by further treatment with isopropanol and deionised water. Solder and flux contaminations were removed without further mechanical cleaning. The adhesive strength of screen-printed metalisation layers increased from 12.50 ± 3.83 MPa without initial cleaning to 21.71 ± 1.85 MPa. We conclude that cleaning procedures during manufacturing of AIMDs, especially the understanding of applicability and limitations, is of central importance for their reliable and longevity.

Reliability of Neural Implants-Effective Method for Cleaning and Surface Preparation of Ceramics.

Severe visual impairment can result from retinal degenerative diseases such as retinitis pigmentosa, which lead to photoreceptor cell death. These pathologies result in extensive neural and glial remodelling, with survival of excitable retinal neurons that can be electrically stimulated to elicit visual percepts and restore a form of useful vision. The Phoenix Bionic Eye is a fully implantable visual prosthesis, designed to stimulate the retina from the suprachoroidal space. In the current study, nine passive devices were implanted in an ovine model from two days to three months. The impact of the intervention and implant stability were assessed using indirect ophthalmoscopy, infrared imaging, and optical coherence tomography to establish the safety profile of the surgery and the device. The biocompatibility of the device was evaluated using histopathological analysis of the tissue surrounding the electrode array, with a focus on the health of the retinal cells required to convey signals to the brain. Appropriate stability of the electrode array was demonstrated, and histological analysis shows that the fibrotic and inflammatory response to the array was mild. Promising evidence of the safety and potential of the Phoenix Bionic Eye to restore a sense of vision to the severely visually impaired was obtained.

Implantation and long-term assessment of the stability and biocompatibility of a novel 98 channel suprachoroidal visual prosthesis in sheep.

The data presented here are related and supplementary data to the research article "Implantation and long-term assessment of the stability and biocompatibility of a novel 98 channel suprachoroidal visual prosthesis in sheep" [1]. In Eggenberger et al., nine sheep of the Suffolk (N=2) and Dorper (N=7) breeds were implanted in the left eye with an electrically inactive, suprachoroidal retinal stimulator (Bionic Eye) for durations of up to 100 days. The surgical safety, implant stability and device biocompatibility were assessed. Intraocular pressure measurements, indirect and infrared ophthalmoscopy and optical coherence tomography were performed at fixed time points to evaluate the clinical effects of the surgery and device implantation. Post-mortem eye tissue collection and histology was performed to measure the effects of the intervention at the cellular level. The data, including a comprehensive collection of fundus, infrared, optical coherence tomography and histology images can be used as a reference for comparison with other research, for example, active retinal stimulators. Furthermore, these data can be used to evaluate the suitability of the sheep model, in particular Dorper sheep, for future research.

Article	Year
Long-term anesthetic protocol in rats: feasibility in electrophysiology studies in visual prosthesis. Veterinary ophthalmology\| PubMed ID: 29148158	2018
Visual prostheses, optogenetics, stem cell and gene therapies: splitting the cake. Neural regeneration research\| PubMed ID: 29863005	2018
Mediating Retinal Ganglion Cell Spike Rates Using High-Frequency Electrical Stimulation. Frontiers in neuroscience\| PubMed ID: 31114476	2019
Prediction of Individual Cochlear Implant Recipient Speech Perception With the Output Signal to Noise Ratio Metric. Ear and hearing\| PubMed ID: 32053546	2020
Editorial: A Conversation With the Brain: Can We Speak Its Language? Frontiers in neuroscience\| PubMed ID: 32922253	2020
Reliability of Neural Implants-Effective Method for Cleaning and Surface Preparation of Ceramics. Micromachines\| PubMed ID: 33669493	2021
Implantation and long-term assessment of the stability and biocompatibility of a novel 98 channel suprachoroidal visual prosthesis in sheep. Biomaterials\| PubMed ID: 34768150	2021
Safety and biocompatibility of a bionic eye: Imaging, intraocular pressure, and histology data. Data in brief\| PubMed ID: 34988269	2021

Gregg Suaning

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