Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a Feline Model of Retinal Degeneration

Abstract

PURPOSE. Retinal prostheses have emerged as a promising technology to restore vision in patients with severe photoreceptor degeneration. To better understand how neural degeneration affects the efficacy of electronic implants, we investigated the function of a suprachoroidal retinal implant in a feline model. METHODS.Unilateral retinal degeneration was induced in four adult felines by intravitreal injection of adenosine triphosphate (ATP). Twelve weeks post injection, animals received suprachoroidal electrode array implants in each eye, and responses to electrical stimulation were obtained using multiunit recordings from the visual cortex. Histologic measurements of neural and glial changes in the retina at the implant site were correlated with cortical thresholds from individual stimulating electrodes.RESULTS. Adenosine triphosphate-injected eyes displayed changes consistent with mid-to-late stage retinal degeneration and remodeling. A significant increase in electrical charge was required to induce a cortical response from stimulation of the degenerated retina compared to that in the fellow control eye. Spatial and temporal characteristics of the electrically evoked cortical responses were no different between eyes. Individual electrode thresholds varied in both the control and the ATP-injected eyes and were correlated with ganglion cell density. In ATP-injected eyes, cortical threshold was also independently correlated with an increase in the extent of retinal gliosis.CONCLUSIONS. These data suggest that even when ganglion cell density remains unaffected, glial changes in the retina following degeneration can influence the efficacy of suprachoroidal electrical stimulation. A better understanding of how glial change impacts retinal prosthesis function may help to further the optimization of retinal implants.

Neural Responses to Multielectrode Stimulation of Healthy and Degenerate Retina

“…The procedure for inducing unilateral retinal degeneration has been previously described in detail. 24,35,37,38 One eye was injected with a 200 lL solution of three parts sterile saline (0.9% NaCl) and one part Dexamethasone (4 mg/ mL), containing approximately 0.2 M (11 mM vitreous concentration) ATP disodium salt (Sigma-Aldrich Corp., St. Louis, MO, USA) to induce photoreceptor degeneration. The fellow eye was a noninjected control.…”

“…This highlights a need to comprehensively evaluate the responses of degenerate retinae to electrical stimulation. 24 Studies in blind human patients have investigated concurrent simulation of pairs, 4,25,26 rows, 5,[27][28][29] or blocks of several electrodes. [30][31][32] The evoked percepts from these types of stimulation strategies have been reported to be variable across trials and patients, suffering from low predictability and dissimilarities between studies.…”

“…This work builds upon a previous study that shows that glial changes in the ATPinjected retina significantly influence the efficacy of singleelectrode stimulation. 24 The cat visual system has long been studied as an analogue for human vision, 34 making the photoreceptor degeneration model ideal for the development of retinal prostheses. 24,35,36 The similarity in size of the cat eye to the human eye also enables clinically relevant electrode size and positioning, with a similar level of photoreceptor degeneration and remodeling to that seen in humans with retinitis pigmentosa.…”

“…24 The cat visual system has long been studied as an analogue for human vision, 34 making the photoreceptor degeneration model ideal for the development of retinal prostheses. 24,35,36 The similarity in size of the cat eye to the human eye also enables clinically relevant electrode size and positioning, with a similar level of photoreceptor degeneration and remodeling to that seen in humans with retinitis pigmentosa. 36 Blindness was induced by intravitreal injection of ATP in a single eye, allowing comparison of healthy and degenerate retinae in the same animal.…”

“…36 Blindness was induced by intravitreal injection of ATP in a single eye, allowing comparison of healthy and degenerate retinae in the same animal. 24 As such, the ATPinjected cat model is ideal for investigating cortical responses to simultaneous stimulation of multiple retinal electrodes, which previous in vivo studies have not explored. As a first step toward understanding the reasons behind the variability seen in patients and to determine how current focusing and steering can be applied to degenerate retinae effectively, the aim of this study was to examine how loss of photoreceptors influences the cortical responses to multielectrode stimulation.…”