Assessment of vision restoration strategies in ex vivo photoreceptor-degenerated mouse retina using microelectrode array

Abstract

Millions of people worldwide suffer from retina degeneration pathologies. To this day the only clinically approved treatment for these pathologies are retina implants. However, state of the art implants fail to rescue vision beyond the level of legal blindness. New stimulation strategies are therefore required to improve retina implant performances, and new treatments must be developed to avoid or delay retina degeneration. In this framework, microelectrode arrays represent an optimal platform to investigate vision restoration strategies in vitro. In the dissertation three different studies are included, with the goal of evaluating current approaches to vision restoration and to investigate new solutions to improve artificial vision. (1) I investigated subretinal electrical pulsatile stimulation of photoreceptor-degenerated mouse retina (rd10 strain) using the retina implant ALPHA AMS R3 chip. I demonstrated efficient and safe stimulation with a single 30 μm electrode. I evaluated the charge threshold dependency with electrode size and reported non-monotonic stimulus response relationship. (2) Using a high-density CMOS based microelectrode array, I evaluated spatial and contrast resolution obtained by sinusoidal epiretinal stimulation. I demonstrated reliable and continuous stimulation without fading and axonal stimulation. Using a logistic regression model to analyze RGCs responses with simple shapes stimulation, I demonstrated high accuracy discrimination of spatial object displacement of 32 μm and artificial contrast level of 10%. (3) Evaluating light responsiveness of organotypic retina culture, I contributed to the assessment of the efficacy of HDAC inhibition to improve cone survival in retinitis pigmentosa.