Li Wennan, Haji Ghaffari Dorsa, Misra Rohit, Weiland James D
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, United States.
Front Cell Neurosci. 2022 Aug 12;16:897146. doi: 10.3389/fncel.2022.897146. eCollection 2022.
Retinal prostheses partially restore vision in patients blinded by retinitis pigmentosa (RP) and age-related macular degeneration (AMD). One issue that limits the effectiveness of retinal stimulation is the desensitization of the retina response to repeated pulses. Rapid fading of percepts is reported in clinical studies. We studied the retinal output evoked by fixed pulse trains vs. pulse trains that have variable parameters pulse-to-pulse. We used the current clamp to record RGC spiking in the isolated mouse retina. Trains of biphasic current pulses at different frequencies and amplitudes were applied. The main results we report are: (1) RGC desensitization was induced by increasing stimulus frequency, but was unrelated to stimulus amplitude. Desensitization persisted when the 20 Hz stimulation pulses were applied to the retinal ganglion cells at 65 μA, 85 μA, and 105 μA. Subsequent pulses in the train evoked fewer spikes. There was no obvious desensitization when 2 Hz stimulation pulse trains were applied. (2) Blocking inhibitory GABA receptor increased spontaneous activity but did not reduce desensitization. (3) Pulse trains with constant charge or excitation (based on strength-duration curves) but varying pulse width, amplitude, and shape increased the number of evoked spikes/pulse throughout the pulse train. This suggests that retinal desensitization can be partially overcome by introducing variability into each pulse.
视网膜假体可部分恢复因视网膜色素变性（RP）和年龄相关性黄斑变性（AMD）而失明患者的视力。限制视网膜刺激效果的一个问题是视网膜对重复脉冲的反应脱敏。临床研究报告了感知的快速消退。我们研究了固定脉冲序列与逐脉冲参数可变的脉冲序列所诱发的视网膜输出。我们使用电流钳记录离体小鼠视网膜中视网膜神经节细胞（RGC）的放电。施加了不同频率和幅度的双相电流脉冲序列。我们报告的主要结果如下：（1）增加刺激频率会诱导RGC脱敏，但与刺激幅度无关。当以65μA、85μA和105μA的电流向视网膜神经节细胞施加20Hz的刺激脉冲时，脱敏现象持续存在。序列中的后续脉冲诱发的放电较少。当施加2Hz的刺激脉冲序列时，没有明显的脱敏现象。（2）阻断抑制性GABA受体可增加自发活动，但不会减少脱敏。（3）具有恒定电荷或兴奋性（基于强度 - 持续时间曲线）但脉冲宽度、幅度和形状可变的脉冲序列会增加整个脉冲序列中诱发的每个脉冲的放电次数。这表明通过在每个脉冲中引入变异性可以部分克服视网膜脱敏。
