gms | German Medical Science

Objective: To enhance the electrode-retina interface for subretinal electrical (e-) stimulation, the functionality of the retinal circuit at the onset of Retinitis Pigmentosa (RP) has been investigated. In our novel approach RP affected degenerated dormant cone photoreceptors (d-Phrs) were e-stimulated.

Materials and Methods: D-Phrs of the rd1 mouse retina were e-stimulated in subretinal configuration by a single platinum/iridium electrode. In simultaneous multilayer recordings, the d-Phrs (calcium-imaging) and ganglion cells (GCs, MEA-recording) activity were recorded. The compositions of the retinal network signalling upon e-activation of d-Phrs were identified by application of respective drugs.

Results: The e-stimulated d-Phrs of rd1 mouse promote network mediated GC activity in the blind retina: 1) D-Phrs responded to e-stimulation and modulated retinal network activity. 2) The vertical retina-signalling is synaptic: Inhibition of voltage gated calcium channels and glutamate-signalling abolished GC responses. In contrary, blocking GABAergic inhibition leads to significant increased GC activity. 3) Cell networks coupled via gap junctions promoted the lateral spread of the evoked activity in outer (~ 60 µm) and inner (~ 120 µm) retina. 4) Subtypes of activated GCs were identified as members of ON, OFF and ON/OFF classes.

Discussion: The d-Phrs can serve as an efficient interface for e-subretinal implants to elicit visual responses. Furthermore, the intact circuity of the blind retina in early RP stage is tempting to be considered as target for implantation of e-subretinal implants in young patients for a transition from blinding to chip-aided vision.

Funding: Haq by Hector Fellow Academy, Basavaraju and Speck by Kerstan Foundation.