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Evelyne Sernagor, Cyril G. Eleftheriou, Jonas Zimmermann, Henrik Kjeldsen, Yael Hanein, Moshe David Pur; Towards The Development Of Carbon Nanotube-based Retinal Implant Technology: Electrophysiological And Ultrastructural Evidence Of Time-dependent Coupling Increase At The Biohybrid Interface. Invest. Ophthalmol. Vis. Sci. 2012;53(14):298.
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One of the many challenges in the development of retinal 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 highly corrosive physiological environment. We investigated the suitability of carbon nanotube (CNT - an advanced material with high biocompatibility and superior electrical properties) electrodes for prolonged repetitive stimulation of retinal ganglion cells (RGCs).
Experiments were performed on retinal wholemounts isolated from the Cone rod homeobox (Crx) KO mouse, a model of Leber congenital amaurosis. Retinas were isolated between birth and 5 months postnatal (photoreceptor degeneration occurs between 1 and 6 months postnatal). Retinas were placed on 60 channels CNT multielectrode arrays (MEAs) (or on commercial titanium nitride (Tin) electrodes for comparison), RGC layer facing down onto the electrodes. RGCs were stimulated using biphasic charge-balanced current pulses. In a subset of experiments, retinas were maintained alive on the MEA for two days to establish whether the stimulation thresholds change over time. Transmission electron microscopy (TEM) was used to visualize the CNT-retina interface.
Stimulation thresholds increased with retinal degeneration both for CNT and for TiN electrodes, suggesting glial proliferation at the interface. However, thresholds were significantly lower at all ages for CNT electrodes. Moreover, the amplitudes of the signals increased with time in CNT (but not in TiN) MEAs. In two-day experiments, stimulation of the same electrodes using the same stimulation parameters on Day 2 yielded significantly lower stimulation thresholds and recruited more RGCs in CNT MEAs, suggesting that coupling between the tissue and the electrodes becomes stronger with time. TEM visualization of the interface revealed intimate contacts between CNTs and the tissue, including engulfment of CNT islands by the retina and CNT penetration towards the RGC layer.
Our results demonstrate that the retina grows towards CNTs with time, resulting in better coupling at the interface. We conclude that CNTs are a promising material for inclusion in retinal prosthetic devices.
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