Using Micro-Electrode-Array Recordings and Retinal Disease Models to Elucidate Visual Functions: Simultaneous Recording of Local Electroretinograms and Ganglion Cell Action Potentials Reveals the Origin of Retinal Oscillatory Potentials

Author:

Haq Wadood1ORCID,Zrenner Eberhart1,Ueffing Marius1ORCID,Paquet-Durand François1ORCID

Affiliation:

1. Centre for Ophthalmology, Institute for Ophthalmic Research, Elfriede-Aulhorn-Straße 7, 72076 Tuebingen, Germany

Abstract

Background: The electroretinogram (ERG) is an essential diagnostic tool for visual function, both in clinical and research settings. Here, we establish an advanced in vitro approach to assess cell-type-specific ERG signal components. Methods: Retinal explant cultures, maintained under entirely controlled conditions, were derived from wild-type mice and rd10 rod- and cpfl1 cone-degeneration mouse models. Local micro-ERG (µERG) and simultaneous ganglion cell (GC) recordings were obtained from the retinal explants using multi-electrode arrays. Band-pass filtering was employed to distinguish photoreceptor, bipolar cell, amacrine cell (AC), and GC responses. Results: Scotopic and photopic stimulation discriminated between rod and cone responses in wild-type and mutant retina. The 25 kHz sampling rate allowed the visualization of oscillatory potentials (OPs) in extraordinary detail, revealing temporal correlations between OPs and GC responses. Pharmacological isolation of different retinal circuits found that OPs are generated by inner retinal AC electrical synapses. Importantly, this AC activity helped synchronise GC activity. Conclusion: Our µERG protocol simultaneously records the light-dependent activities of the first-, second-, and third-order neurons within the native neuronal circuitry, providing unprecedented insights into retinal physiology and pathophysiology. This method now also enables complete in vitro retinal function testing of therapeutic interventions, providing critical guidance for later in vivo investigations.

Funder

Hector Fellow Academy

Tistou and Charlotte Kerstan Foundation

Zinke heritage foundation

Deutsche Forschungsgemeinschaft

Open Access Publishing Fund of the University of Tübingen

Publisher

MDPI AG

Subject

Bioengineering

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