Microelectronic Retinal Prostheses Research Articles

Response Profiles of Retinal Ganglion Cells to Sinusoidal Electric Stimulation vary for Low vs. High Frequencies.

Microelectronic retinal prostheses electrically stimulate retinal neurons with the goal of restoring vision in patients blinded by outer retinal degeneration. Despite some success in clinical trials, the quality of vision elicited by these devices is still limited. To improve the performance of retinal prostheses, our group studied how retinal neurons respond to electric stimulation. Our previous work showed that responses of retinal ganglion cells (RGCs) are frequency-dependent and different types of RGCs can be preferentially activated with a specific frequency and current amplitude. In the present study, we systemically examined responses of RGCs to sinusoidal electric stimulation with varying frequencies and amplitudes. We found that ON sustained alpha RGCs show distinct stimulus-response relationships to low and high frequency stimulation. For example, RGCs showed monotonic response curves to 500 Hz sinusoidal stimulation, whereas they showed non-monotonic response curves to 2000 Hz stimulation. We also described how increasing stimulus frequency gradually changed the response curves of RGCs.

Network-mediated responses of ON ganglion cells to electric stimulation become less consistent across trials during retinal degeneration.

Microelectronic retinal prostheses are being developed to restore sight in individuals blinded by outer retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Unfortunately, the quality of vision restored by these devices is still limited. To improve the quality of elicited vision, our group studies the responses of retinal neurons to electric stimulation. Our previous work showed that responses mediated through the retinal network are reproducible with high temporal precision, even for spikes that occur >100 ms after stimulus onset. Because they arise through the network, it is important to understand whether such reliability changes in the degenerate retina. Here, we examined response variability at several different stages of degeneration: postnatal day 14 (P14), P18, P31 and P60 in a well-established mouse model of degeneration (rd10). Spiking responses of ON alpha RGCs were recorded multiple times to an identical electric stimulus. We found that the trial-to-trial variability increased over the course of retinal degeneration. This finding may help to explain the reported variability in the quality of elicited vision across subjects using these devices.

Efficacy of electrical stimulation of retinal ganglion cells with temporal patterns resembling light-evoked spike trains.

People with degenerative retinal diseases such as retinitis pigmentosa lose most of their photoreceptors but retain a significant proportion (~30%) of their retinal ganglion cells (RGCs). Microelectronic retinal prostheses aim to bypass the lost photoreceptors and restore vision by directly stimulating the surviving RGCs. Here we investigate the extent to which electrical stimulation of RGCs can evoke neural spike trains with statistics resembling those of normal visually-evoked responses. Whole-cell patch clamp recordings were made from individual cat RGCs in vitro. We first recorded the responses of each cell to short sequences of visual stimulation. These responses were converted to trains of electrical stimulation that we then presented to the same cell via an epiretinal stimulating electrode. We then quantified the efficacy of the electrical stimuli and the latency of the evoked spikes. In all cases, spikes were evoked with sub-millisecond latency (0.55 ms, median, ON cells, n = 8; 0.75 ms, median, OFF cells, n = 6) and efficacy ranged from 0.4-1.0 (0.79, median, ON cells; 0.97, median, OFF cells). These data demonstrate that meaningful spike trains, resembling normal responses of RGCs to visual stimulation, can be reliably evoked by epiretinal prostheses.

Image Analysis for Microelectronic Retinal Prosthesis

By way of extracellular, stimulating electrodes, a microelectronic retinal prosthesis aims to render discrete, luminous spots-so-called phosphenes-in the visual field, thereby providing a phosphene image (PI) as a rudimentary remediation of profound blindness. As part thereof, a digital camera, or some other photosensitive array, captures frames, frames are analyzed, and phosphenes are actuated accordingly by way of modulated charge injections. Here, we present a method that allows the assessment of image analysis schemes for integration with a prosthetic device, that is, the means of converting the captured image (high resolution) to modulated charge injections (low resolution). We use the mutual-information function to quantify the amount of information conveyed to the PI observer (device implantee), while accounting for the statistics of visual stimuli. We demonstrate an effective scheme involving overlapping, Gaussian kernels, and discuss extensions of the method to account for shortterm visual memory in observers, and their perceptual errors of omission and commission.

Retinal replacement--the development of microelectronic retinal prostheses--experience with subretinal implants and new aspects.

Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. Different concepts of retinal replacement are currently under investigation. The aim of the retinal prostheses is to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. Within the field of visual prosthetic developments mainly two retinal based concepts are under investigation. One of the concepts is the epiretinal implant which acquires images of an external camera and after preprocessing by a computer reading this visual information into the human visual system. In the subretinal prosthesis design concept an array of stimulation electrodes is placed in the subretinal space. True to the concept the image falling on the retina and its light impulses are converted into electrical currents by microphotodiodes and the retina is stimulated with these locally. To test the feasibility of the concepts the biocompatibility and to determine basic stimulation parameters a lot of animal experiments and first human experiments were carried out. Currently the research conducted by teams in Germany, the USA and Japan into epiretinal and subretinal implants has reached the stage where clinical trials can now be performed. Individual pilot studies were carried out for both the epiretinal and the subretinal implant by different research groups. The results achieved by the researchers indicate that cortical action potentials can be triggered by electric retinal stimulation with both concepts. The experimental work has highlighted a whole range of obstacles, not all of which have yet been fully resolved. These findings offer hope that coarse restoration of vision may be feasible by electrical stimulation.

Visual perception in a blind subject with a chronic microelectronic retinal prosthesis

A retinal prosthesis was permanently implanted in the eye of a completely blind test subject. This report details the results from the first 10 weeks of testing with the implant subject. The implanted device included an extraocular case to hold electronics, an intraocular electrode array (platinum disks, 4 × 4 arrangement) designed to interface with the retina, and a cable to connect the electronics case to the electrode array. The subject was able to see perceptions of light (spots) on all 16 electrodes of the array. In addition, the subject was able to use a camera to detect the presence or absence of ambient light, to detect motion, and to recognize simple shapes.