Dynamic range of safe electrical stimulation of the retina

Electronic retinal prostheses represent a potentially effective approach for restoring some degree of sight in blind patients with retinal degeneration. However, levels of safe electrical stimulation and the underlying mechanisms of cellular damage are largely unknown. We measured the threshold of cellular damage as a function of pulse duration, electrode size, and number of pulses to determine the safe range of stimulation. Measurements were performed in-vitro on embryonic chicken retina with saline-filled glass pipettes for stimulation electrodes. Cellular damage was detected using Propidium Iodide fluorescent staining. Electrode size varied from 115 mu m to 1mm, pulse duration from 6 mu s to 6ms, and number of pulses from 1 to 7,500. The threshold current density was independent of electrode sizes exceeding 400 mu m. With smaller electrodes the current density was scaling reciprocal to the square of the pipette diameter, i.e. acting as a point source so that the damage threshold was determined by the total current in this regime. The damage threshold current measured with large electrodes (1mm) scaled with pulse duration as t(-0.5), which is characteristic of electroporation. For repeated electrical pulsed exposure on the retina the threshold current density varied between 0.059 A/cm2 at 6ms to 1.3 A/cm2 at 6 mu s. The dynamic range of safe stimulation, i.e. the ratio of damage threshold to stimulation threshold was found to be duration-dependent, and varied from 10 to 100 at pulse durations varying between 10 mu s to 10ms. Maximal dynamic range of 100 was observed near 1ms pulse durations.