Abstract
Purpose :
Significant interest exists in developing electric field (EF) application into a technology to direct target-specific neuronal regeneration. We have shown that in vivo EF stimulation of the rat optic nerve (ON) after crush injury directed full-length regeneration of retinal ganglion cell axons and partial restoration of vision. Whether EFs can successfully direct axon regeneration in humans is unknown. Here, we pair 3D computational modeling experiments with cadaveric measurements to interrogate the optimal electrode configuration for generating an EF along the human ON.
Methods :
High-resolution 3D image of the adult head and orbit was developed using computed tomography, then discretized and imported into the Admittance Method computational platform. Various combinations of stimulating electrodes (SE) and ground electrodes (GE) were modeled and the field gradient estimated. Electrodes were then surgically placed in cadavers. SEs considered included a contact lens (CL) or intraorbital J-electrode, needle electrode, or cuff electrode. GEs included a needle electrode on the optic chiasm,small (4x4cm) and large patch (9x9cm) along the occiput. Eight measuring electrodes were placed at intervals along the ON.
Results :
3D modeling predicted that direct electrodes placed along the optic nerve will generate a larger electric gradient than indirect electrodes placed on the surface of the head. Cadaveric experiments (n=2) accordingly showed a 1.54 V/m gradient with direct stimulation, compared to 1.16 and 0.9 V/m with indirect stimulation. This was similar to prior rat measurements which demonstrated a gradient of 1.4 - 1.7 V/m.
Conclusions :
Given that we were able to generate similar EF gradients in human cadavers as rats, we are optimistic about the potential for translation. Further work will be aimed at development of wearable devices for EF stimulation of the human ON.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.