Subretinal Microphotodiode Arrays: A Promising Road to Restitution of Vision in Degeneration of the Outer Retina

Abstract

Abstract: : Purpose: To develop a subretinal prosthesis to replace the function of lost photoreceptors in diseases like retinitis pigmentosa and age-related macular degeneration. Methods: Subretinal stimulation devices, currently under development, consist of an array (3 x 3 mm) of 1600 microphotodiodes on a polyimide foil strip with electronic components to receive and store additional energy and to control electrical stimulation of retinal neurons via TiN-electrodes (for a review see E. Zrenner, Science 295, 1022-1025, 2002). To evaluate stimulus parameters wire-bound devices with electrode arrays have been implanted in pigs, rabbits and cats via a novel ab externo and an ab interno access to the subretinal space. Results: Multichannel microelectrode recordings of visual cortical activities, evoked by electrical retina stimulation (EECP) show retinotopically correct cortical activation in cats in acute and chronic preparations. Estimated spatial resolution is about 0.9° of visual angle. Threshold for EECPs in rabbits is as low as 3 nC per electrode and pulse (F. Gekeler et al., in prep.). Intrinsic signal optical imaging of the cat visual cortex has confirmed the function and achievable spatial resolution of the subretinal device (U. Eysel et al., in prep). On the basis of in vitro tests in healthy and degenerated retinae a resolution of 0.5° of visual angle and retinal threshold as low as 0.5 nC per electrode can be expected (A. Stett et al., Vision Res. 40, 1785-1795; 2000). Histology was performed in rabbits, pigs, and cats up to 29 months post-operatively. The retina tolerates the chip well, showing good embedment of the silicon device and preserved retinal architecture on top of the chip (K. Kohler et al., Ophthalmologe 98, 364-368, 2001) Conclusions: Several objective methods in animal experiments have proven that subretinal implants can activate the visual system in a spatially correct manner. The retina overlying the implant showed no signs of degeneration which would interfere with function. It therefore can be assumed that the concept of a subretinal visual prosthesis will be useful in helping patients blind from degenerative retinal diseases.

Keywords: electrophysiology: non-clinical • retina • retinal connections, networks, circuitry