Feasibility study for a glutamate driven subretinal prosthesis: local subretinal application of glutamate on blind retina evoke network-mediated responses in different types of ganglion cells

Abstract

Objective. A feasibility study for a transmitter based subretinal prosthesis, generating visual responses in blind mouse retina is presented. Approach. Degenerated rd1 mouse retina were stimulated in subretinal configuration by local glutamate (Glu) or NMDA application via micropipettes (~1.5 μm) and thereby the outer retinal activity was recorded by calcium-imaging or the ganglion cell (GC) activity was recorded by the multi-electrode array system. The network mediated activation of GC via bipolar cells was approved by the administration of Glu receptor blockers. Main results. Data of the degenerated and blind rd1 mouse retina reveals that the outer retina is Glu sensitive and that the subretinal Glu stimulation promotes network mediated GC responses. Analysis of the spatial activity-spread indicates that the Glu induced cell activation radius in the outer retina (~12.5 μm) and postsynaptically activated GC (~40 μm) is focal to the stimulation pipette tip. Moreover, the application of NMDA in subretinal space also evoked network mediated GC responses. The Glu-activated GC were identified as ON–OFF, OFF and two ON cells types. Significance. This study evaluates the prerequisite for the function of a transmitter based implant, that after the loss of the photoreceptors, the remnant blind retinal network is Glu sensitive and functional, positively. The differential activation of ON (hyperpolarisation) and OFF (depolarisation) bipolar cells by transmitter Glu is a unique feature and of high interest for retinal implants. Therefore, the respective bipolar cell types could only be driven by glutamatergic stimulation accurately and not by electrical stimulation. The preserved functionality of the blind retina at the onset of complete blindness is motivating to continue research on a transmitter-based prosthesis. Since the artificial Glu stimulation mimics the natural retinal input, early implantation of a Glu-prosthesis might delay the devastating retinal remodelling positively, due to the neuronal-plasticity.