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| Book/Dissertation / PhD Thesis | FZJ-2021-01392 |
2021
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
Jülich
ISBN: 978-3-95806-553-6
Please use a persistent id in citations: http://hdl.handle.net/2128/28431 urn:nbn:de:0001-2021080905
Abstract: With the ultimate goal to restore vision in blind patients, visual prostheses have been developed tointerface and modulate the electrical activity of different neuronal structures along the visualpathway, targeting mainly the visual cortex, the optic nerve, and the retina. Thus, prostheticdevices that stimulate electrically the retina have been employed to treat blind patients with retinaldegenerative diseases such as age-related macular degeneration and retinitis pigmentosa, whichcomprise the third leading cause of blindness worldwide. In the last decades, the development ofretinal implants with commercial approval and those used in clinical trials has shown meaningfulprogress towards the restoration of useful vision. Nonetheless, the recent withdrawal of currentretinal implants from the market exhorts the scientific community to join and enhance efforts toimprove the technology and the efficiency of such devices to achieve further steps in the restorationof vision.Aiming at a new generation of retinal implants, the BiMEA consortium has proposed thedevelopment of a bidirectional microelectrode array (BiMEA) to enable a bidirectionalcommunication with the retina. To this end, penetrating neural probes were proposed to allowaccess to the intraretinal space and to modulate and record simultaneously the electrical activity ofthe retina. To further develop the BiMEA strategy, this work exposes the development and in vitrovalidation of BiMEA probes, setting in turn the groundwork for the future development of novelintraretinal implants.First, the BiMEA concept was validated in healthy and degenerated ex-planted mouse retinas usingsilicon-based devices, thereby demonstrating the feasibility of a bidirectional communicationbetween the retina and a prosthetic device. Thus, the stimulation of the inner retina with safeelectrical stimuli while recording the neuronal activity of the output neurons of the retina, theganglion cells, was achieved. Going a step further, intraretinal devices based on flexible materialswere developed and optimized to better match the anatomy and the mechanical properties of theretina while fulfilling the insertion requirements of such devices. Hence, flexible intraretinalprobes with miniaturized shanks 7 μm thick and 145 μm long were successfully inserted into thethin retina. As a result, local field potentials and the spiking activity of both, healthy anddegenerated retinas, were recorded. Moreover, electrically evoked potentials were captured afterapplying charge densities as low as 81.5 μC/cm2.Furthermore, a systematic study to validate the acute performance of both silicon and flexibleBiMEAs was conducted. This study revealed that flexible penetrating probes based onparylene-C with a shank width as narrow as 50 μm diminished the acute insertion footprint ofintraretinal probes, inducing lesions nearly 2.5 times the cross-section of the probe. Moreover,electrical recordings had a maximum signal-to-noise ratio of 12.37 and a success rate of insertionof 93%. Consequently, the development of intraretinal devices open the door for closed loopfeedback systems, offering the possibility to track and acknowledge in situ the electrical activityof the retina and the success of the stimulation while adjusting accordingly the stimuli. Even more,aiming future in vivo applications, flexible BiMEA probes showed the potential for thedevelopment of intraretinal implants.
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