Purchase this article with an account.
SeongKwang Cha, JungRyul Ahn, Yongsook Goo; Degeneration Stage-specific Safe Limit for Electric Stimulus in rd10 Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4198.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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, there is a possibility of neural damage with repetitive electric stimulus. 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.
Rd10 mice with postnatal weeks (PNWs) 6.5, 10, 20 and 34 were chosen for different degeneration stages (n=3 for each PNW). After isolation of retinal explant, RGC side is attached on the electrode. By applying electric pulses (500 μs-long, 30 μA-amplitude, cathodic phase-first, biphasic charge-balanced, symmetric square current with 5 Hz frequency) for 450 min, we recorded responses of RGC spikes with 8 × 8 perforated multi-electrode array (pMEA). Our in vitro system mimics the configuration of epiretinal prosthesis. We compared RGC spike rate at 25, 70, 135, 220, 325, and 450 min of electric stimulus application.
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). But the rate of frequency change differed in each PNW group; in PNW 34 group, frequency change of RGC spikes were observed at 25 min of stimulus application (p<0.05), while 135 min of stimulus application induced frequency change in PNW 6.5 and 10 group (p<0.01). The multiple peaks in post-stimulus time histogram which are correlated with phase-locking local field potential disappeared after the 135~325 min of electric stimulus application; the disappearance timing is different in different PNW groups.
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, degeneration stage-specific long-term safety limit should be considered to establish optimal vision restoration strategies using retinal prosthesis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only