Developing a new generation of neuro-prosthetic interfaces: structure-function correlates of viable retina-CNT biohybrids

Abstract

One of the many challenges in the development of neural prosthetic devices is the choice of electrode material. Electrodes must be biocompatible, and at the same time, they must be able to sustain repetitive current injections in a highly corrosive physiological environment. We investigated the suitability of carbon nanotube (CNT) electrodes for retinal prosthetics by studying prolonged exposure to retinal tissue and repetitive electrical stimulation of retinal ganglion cells (RGCs). Experiments were performed on retinal wholemounts isolated from the Cone rod homeobox (CRX) knockout mouse, a model of Leber congenital amaurosis. Retinas were interfaced at the vitreo-retinal juncture with CNT assemblies and maintained in physiological conditions for up to three days to investigate any anatomical (immunohistochemistry and electron microscopy) and electrophysiological changes (multielectrode array stimulation and recordings; electrodes were made of CNTs or commercial titanium nitride). Anatomical characterisation of the inner retina, including RGCs, astrocytes and Müller cells as well as cellular matrix and inner retinal vasculature, provide strong evidence of a gradual remodelling of the retina to incorporate CNT assemblies, with very little indication of an immune response. Prolonged electrophysiological recordings, performed over the course of three days, demonstrate a gradual increase in signal amplitudes, lowering of stimulation thresholds and an increase in cellular recruitment for RGCs interfaced with CNT electrodes, but not with titanium nitride electrodes. These results provide for the first time electrophysiological, ultrastructural and cellular evidence of the time-dependent formation of strong and viable bio-hybrids between the RGC layer and CNT arrays in intact retinas. We conclude that CNTs are a promising material for inclusion in retinal prosthetic devices.