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Dae-jin Park, Jeong yeol Ahn, Yongsook Goo, Retina; Finding stage-specific degenerative patterns of retinal ganglion cell (RGC) firing in rd10 mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):773.
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© ARVO (1962-2015); The Authors (2016-present)
Mammalian retinal degenerations show different physiological features in each progression stage. In this study, retinal degenerative changes and response characteristics to electrical stimuli are investigated according to each stage. The stage-specific response may provide us the guideline for optimal time window for the implement of retinal prosthesis.
After isolating retina from rd10 mice, good animal model for RP, retinal patch was placed retinal ganglion cell (RGC) layer down onto 8x8 multi-electrode arrays (MEA). Spontaneous and electrically-evoked RGC spikes were recorded at postnatal week (PNW) 2 to 34. Cathodic phase-first biphasic current pulses (sine or square pulse) were applied (duration: 500 µs, amplitude: 5 ~ 60 µA, frequency: 1~20 Hz). Mean frequency of RGC spikes, 2nd peak latency of inter-spike interval histogram, power spectral density, correlation index, evoked RGC spike number and valid response ratio (VRR) were compared among each age group. We defined VRR as RGC spike numbers in post-stimulus 100 ms / those in post-stimulus 1000 ms since among multiple peaks in PSTH, the dominant peak is observed around 100 ms, like in wild-type mice.
Mean frequency of RGC spike is the highest at PNW4.5 (p<0.001). Inter-burst intervals linearly increase after PNW4.5 and reach the maxima (200 ms) at PNW26 (p<0.001). During electrical stimulation, mean frequency of RGC spike and oscillatory local field potentials are fixed to 15~20 and 10~13 Hz, respectively. Evoked spike numbers in post-stimulus 100 ms linearly increase and stabilize after PNW6.5. VRR is the lowest at PNW3~4.5 and stabilized after PNW6.5 (p<0.001).
Our results might be a reflection of the rapid rod photoreceptor degeneration during PNW3~4.5 and synaptic changes after PNW6.5. In PNW3~4.5, RGC spontaneous firing is the highest and VRR is the lowest, which suggest the therapeutic potential with retinal prosthesis during this period may be not so good because 1st peak at 100 ms in PSTH is less dominant. 5 Hz oscillatory rhythm observed after PNW6.5, well known property in rd mice retina, is a major cause of poor signal-to-noise ratio for visual perception. However, since VRRs are relatively high between PNW6.5~20, we suggest that this period would be a good time window for prosthesis implement.
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