Abstract
Purpose :
Retinal prostheses have been developed to restore vision for the blind with retinitis pigmentosa (RP) and age-related macular degeneration (AMD) by electrical stimulation of surviving neurons, eliciting spikes of retinal ganglion cells (RGCs). While electric stimulus can evoke RGC spikes, possibility of neural damage is coincided with electrical stimulation. Therefore, determining the safe limit for electric stimulus is important for the successful development of the retinal prostheses. Here, we explored degeneration stage-specific safe limit for electric stimulus in rd10 mouse, a good animal model of human RP.
Methods :
Rd10 mice with postnatal weeks (PNWs) 6.5, 10, 20 and 34 were chosen for different degeneration stages (n=3 for each PNW). For control groups, we choose WT mice with PNW 10 (n=3). After isolation of retinal explant, RGC side is attached on the 8 × 8 perforated multi-electrode array (pMEA), which mimics the configuration of epiretinal prosthesis. Electricstimulus with 5 Hz frequency (500 μs-long, 30 μA-amplitude, cathodic phase-first, biphasic charge-balanced, symmetric square current) were applied for 455 min.
Results :
In all PNW groups, pMEA system enabled us a stable recording of RGC spikes up to 480 min. In all PNW groups except PNW 20, the mean frequency of RGC spikes decreased with increasing stimulus duration (p<0.001). The difference of mean firing rate between first 5 (0~5) min and last 5 (450~455) min of the stimulus duration were 7.38 ± 1.12, 4.14 ± 0.75, 1.19 ± 0.80, 9.73 ± 0.83 and 8.92 ± 0.66 spike number/sec in PNW 6.5, 10, 20, 34 and WT respectively. However, the slope of frequency decrement differed according to PNW group; abrupt frequency decrement at 25 min, 135 min, and 225 min for PNW 34, 6.5, and 10, respectively. With electric stimulus, WT retina shows steeper frequency decrement than degenerated retinae (p<0.05).
Conclusions :
These results imply that safe limit for electric stimulus is different at each degeneration stage. The difference of safe limit could be explained by different retinal network and Mueller cell thickness according to degeneration stage. Thus, long-term safety limit of degenerated retina should be considered to establish optimal vision restoration strategies using retinal prosthesis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.