High spatial resolution artificial vision inferred from the spiking output of retinal ganglion cells stimulated by optogenetic and electrical means

Abstract

With vision impairment affecting millions of people world-wide, various strategies aiming at vision restoration are being undertaken. Thanks to decades of extensive research, electrical stimulation approaches to vision restoration began to undergo clinical trials. Quite recently, another technique employing optogenetic therapy emerged as a possible alternative. Both artificial vision restoration strategies reported poor spatial resolution so far. In this article, we compared the spatial resolution inferred ex vivo under ideal conditions using a computational model analysis of the retinal ganglion cell (RGC) spiking activity. The RGC spiking was stimulated in epiretinal configuration by either optogenetic or electrical means. RGCs activity was recorded from the ex vivo retina of transgenic late-stage photoreceptor-degenerated mice (rd10) using a high-density Complementary Metal Oxide Semiconductor (CMOS) based microelectrode array. The majority of retinal samples were stimulated by both, optogenetic and electrical stimuli using a spatial grating stimulus. A population-level analysis of the spiking activity of identified RGCs was performed and the spatial resolution achieved through electrical and optogenetic photo-stimulation was inferred using a support vector machine classifier. The best f1 score of the classifier for the electrical stimulation in epiretinal configuration was 86% for 32 micron wide gratings and increased to 100% for 128 microns. For optogenetically activated cells, we obtained high f1 scores of 82% for 10 microns grid width for a photo-stimulation frequency of 2.5 Hz and 73% for a photo-stimulation frequency of 10 Hz. A subsequent analysis, considering only the RGCs modulated in both electrical and optogenetic stimulation protocols revealed no significant difference in the prediction accuracy between the two stimulation modalities. The results presented here indicate that a high spatial resolution can be achieved for electrical or optogenetic artificial stimulation using the activated retinal ganglion cell output.

Avoidance of axonal stimulation with sinusoidal epiretinal stimulation

“…In the same work a radius of activation proportional to the electrode size was reported, potentially superior to the one shown for 25 ms pulses (Weitz et al 2015). Similar results were found using grating stimulation, closely matching the spatial resolution achieved by optogenetic stimulation (Cojocaru et al 2022). These in vitro findings need to be validated in clinical settings.…”

“…There, however, the stimulation was fixed to one frequency (40 Hz) and only a few stimulation amplitudes. Spatially localized stimulation was also reported for epiretinal stimulation using elongated 'grating-like' electrodes at the same frequency (40 Hz) and one single amplitude (Cojocaru et al 2022). Here, we therefore sought to investigate the effect of sinusoidal frequencies up to 100 Hz in epiretinal configuration by electrically imaging (Zeck et al 2017) RGCs in the ex-vivo photoreceptor-degenerated mouse retina.…”

Assessment of chemotherapeutic effects on cancer cells using adhesion noise spectroscopy

“…Cell-cell and cell-extracellular matrix (ECM) protein interactions are essential for proper tissue development, maintenance, and regeneration. Thus, in vitro cells adhere, grow, and perform more physiologically when adhering to surfaces coated with ECM proteins or specific adhesion molecules ( Cruz Walma and Yamada, 2020 ) Both Poly-L-lysine, which is commonly used in neuroscientific applications ( Eickenscheidt and Zeck, 2014 ; Stutzki et al, 2016 ; Cojocaru et al, 2022 ) and Collagen type I as the most abundant ECM protein in our body ( Murata et al, 1986 ; Katsuda et al, 1992 ; Hohenester and Engel, 2002 ) ensure tight tissue adhesion ( Vitale et al, 2018 ). We therefore addressed the biocompatibility of the cited ECM biomolecules ( Prockop and Kivirikko, 1995 ; Vitale et al, 2018 ) by analyzing the viability of the cell line HT-29 cultivated in 96-well plates and on CMOS MEAs coated with Poly-L-lysine or Collagen type I.…”

“…Therefore, cell proliferation is determined by the MEA’s area covered with adherent cells, assuming a loss in cell adhesion due to the cytotoxic anti-cancer drug 5-FU ( Akalovich et al, 2021 ; Fohlen et al, 2021 ). Our MEA comprises both subcellular resolution ( Hierlemann et al, 2011 ; Viswam et al, 2018 ; Ell, Zeitler, et al, 2023 ) and cellular network studies ( Amin et al, 2017 ; Viswam et al, 2017 ; Angotzi et al, 2018 ; Abbott et al, 2022 ; Cojocaru et al, 2022 ; Emery et al, 2022 ; 2023 ). To relate electrical imaging to optical imaging, CAN-based images were overlaid with brightfield microscopy images.…”