Retinal Prosthesis for the Blind

Existing epiretinal implants for the blind are designed to electrically stimulate large groups of surviving retinal neurons using a small number of electrodes with diameters of several hundred micr...

Electrical Stimulation of Mammalian Retinal Ganglion Cells With Multielectrode Arrays

Gelatin has been used for many years in pharmaceutical formulation, cell culture and tissue engineering on account of its excellent biocompatibility, ease of processing and availability at low cost. Over the last decade gelatin has been extensively evaluated for numerous ocular applications serving as cell-sheet carriers, bio-adhesives and bio-artificial grafts. These different applications naturally have diverse physical, chemical and biological requirements and this has prompted research into the modification of gelatin and its derivatives. The crosslinking of gelatin alone or in combination with natural or synthetic biopolymers has produced a variety of scaffolds that could be suitable for ocular applications. This review focuses on methods to crosslink gelatin-based materials and how the resulting materials have been applied in ocular tissue engineering. Critical discussion of recent innovations in tissue engineering and regenerative medicine will highlight future opportunities for gelatin-based materials in ophthalmology.

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Gelatin-Based Materials in Ocular Tissue Engineering.

The Argus II Retinal Prosthesis System

Electric stimulation of the retina reliably elicits light percepts in patients blinded by outer retinal diseases. However, individual percepts are highly variable and do not readily assemble into more complex visual images. As a result, the quality of visual information conveyed to patients has been quite limited. To develop more effective stimulation methods that will lead to improved psychophysical outcomes, we are studying how retinal neurons respond to electric stimulation. The situation in the retina is analogous to other neural prosthetic applications in which a better understanding of the underlying neural response may lead to improved clinical outcomes. Here, we determined which element in retinal ganglion cells has the lowest threshold for initiating action potentials. Previous studies suggest multiple possibilities, although all were within the soma/proximal axon region. To determine the actual site, we measured thresholds in a dense two-dimensional grid around the soma/proximal axon region of rabbit ganglion cells in the flat mount preparation. In directionally selective (DS) ganglion cells, the lowest thresholds were found along a small section of the axon, about 40 μm from the soma. Immunochemical staining revealed a dense band of voltage-gated sodium channels centered at the same location, suggesting that thresholds are lowest when the stimulating electrode is closest to the sodium-channel band. The size and location of the low-threshold region was consistent within DS cells, but varied for other ganglion cell types. Analogously, the length and location of sodium channel bands also varied by cell type. Consistent with the differences in band properties, we found that the absolute (lowest) thresholds were also different for different cell types. Taken together, our results suggest that the sodium-channel band is the site that is most responsive to electric stimulation and that differences in the bands underlie the threshold differences we observed.

Axonal Sodium-Channel Bands Shape the Response to Electric Stimulation in Retinal Ganglion Cells

Comparison of electrical stimulation thresholds in normal and retinal degenerated mouse retina.

Background/Purpose:A safe, effective adhesive could be useful in the management of retinal holes or tears and selected complicated retinal detachments, as well as for attaching a small electronic device (retinal prosthesis) to the retina. In this study, we examined nine commercially available compou

Bioadhesives for intraocular use.

Background and objective To study the heat and power dissipation effect of anintraocular electronic heater on the retina. The determination of thermal parameters that are nonharmful to the retina will aid in the development of an implantable intraocular electronic retinal prosthesis. Materials and methods In dogs, five different retinal areas were touched with a custom intraocular heater probe (1.4 x 1.4 x 1.0 mm) for 1 second while the heater dissipated 0 (control), 10, 20, 50, or 100 mW. In a second protocol, the heater was mechanically held in the vitreous cavity while dissipating 500 mW for 2 hours while monitoring intraocular temperature. The animals were observed for 4 weeks with serial fundus photography and electroretinography. The procedure was then repeated in the fellow eye. The dogs were killed and both eyes were enucleated and submitted for histology. Results In experiments using protocol 1, heater settings of 50 mW or higher caused an immediate visible whitening of the retinal tissue. Histologically, this damage was evident only if the eyeswere immediately enucleated. Permanent damage was caused by heater settings of 100 mW or higher. Under protocol 2, no ophthalmologic, electroretinography, or histologic differences were noted between the groups. Temperature increases of 5 degrees C in the vitreous and 2 degrees C near the retina were noted. Conclusions The liquid environment of the eye acts as a heat sink that is capable of dissipating a significant amount of power. An electronic chip positioned away from the retina can run at considerably higher powers than a chip positioned on the retinal surface.

Heat effects on the retina.

Results: Analysis of EERs revealed distinct early (less than 10 ms) and late (greater than 50 ms) responses. Synaptic blockers abolished the late response but not the early response. For eliciting the early response in normal and rd mice, a square pulse stimulus was more efficient than the sine wave or pulse train. In normal and degenerate canine retina, electrically elicited responses also exhibited early and late phases. EERs in a retinal prosthesis test subject (with retinitis pigmentosa) showed latency similar to the canine, but no evidence of an early response, possibly due to the lack of sensitivity in scalp (human) vs cortical surface (canine) electrode placement. Conclusion: EERs could be elicited from both normal and degenerated retina. Mouse, dog, and human EERs showed common characteristics.

Neural responses elicited by electrical stimulation of the retina.

Experiments were conducted to assess the effect of stimulating electrode parameters (size, position, and waveform shape) on electrically elicited ganglion cell action potentials from isolated rabbit retina. Thirty-eight isolated rabbit retinas were stimulated with bipolar stimulating electrodes (either 125 or 25 mum in diameter) positioned on either the ganglion or the photoreceptor side. Recording electrodes were placed between the optic disc and the stimulating electrodes. Cathodic-first, biphasic, current waveforms of varying pulse durations (0.1, 0.5, 1 ms) were used. For the four conditions tested (125- electrode and 25-mum electrode, ganglion cell, and photoreceptor positions) threshold currents ranged from 6.7 to 23.6 muA, depending on location and pulse duration. With 1-ms pulse duration, no statistically significant difference was seen between threshold currents when either size electrode was used to stimulate either the ganglion cell side or the photoreceptor side. For all groups, the threshold currents using the 1-ms pulse were lower than those using 0.1 ms, but the 0.1-ms pulses used less charge. These experiments provide a number of valuable insights into the relative effects of several stimulation parameters critical to the development of an implanted electronic retinal prosthesis

Shih Jen Chen

Papers

Comparison of electrical stimulation thresholds in normal and retinal degenerated mouse retina.

Bioadhesives for intraocular use.

Heat effects on the retina.

Neural responses elicited by electrical stimulation of the retina.

Electrical Stimulation in Isolated Rabbit Retina