Retinal prostheses aim at restoring partial sight to patients that are blind due to retinal degenerative diseases by electrically stimulating the surviving healthy retinal neurons. Ideally, the electrical stimulation of the retina is intended to induce localized, focused, percepts only; however, some epiretinal implant subjects have reported seeing elongated phosphenes in a single electrode stimulation due to the axonal activation of retinal ganglion cells (RGCs). This issue can be addressed by properly devising stimulation waveforms so that the possibility of inducing axonal activation of RGCs is minimized. While strategies to devise electrical stimulation waveforms to achieve a focal RGCs response have been reported in literature, the underlying mechanisms are not well understood. This article intends to address this gap; we developed morphologically and biophysically realistic computational models of two classified RGCs: D1-bistratified and A2-monostratified. Computational results suggest that the sodium channel band (SOCB) is less sensitive to modulations in stimulation parameters than the distal axon (DA), and DA stimulus threshold is less sensitive to physiological differences among RGCs. Therefore, over a range of RGCs distal axon diameters, short-pulse symmetric biphasic waveforms can enhance the stimulation threshold difference between the SOCB and the DA. Appropriately designed waveforms can avoid axonal activation of RGCs, implying a consequential reduction of undesired strikes in the visual field.

中文翻译：

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视网膜前假体中视网膜神经节细胞的靶向刺激：一项多尺度计算研究

视网膜假体旨在通过电刺激幸存的健康视网膜神经元来恢复因视网膜退行性疾病而失明的患者的部分视力。理想情况下，视网膜的电刺激旨在仅诱导局部、集中的感知；然而，一些视网膜前植入物受试者报告说，由于视网膜神经节细胞 (RGC) 的轴突激活，在单个电极刺激中看到拉长的光幻视。这个问题可以通过适当设计刺激波形来解决，从而最大限度地减少诱导 RGC 轴突激活的可能性。虽然文献中已经报道了设计电刺激波形以实现局灶性 RGC 响应的策略，但其潜在机制尚不清楚。本文旨在解决这一差距；我们开发了两种分类 RGC 的形态学和生物物理学现实计算模型：D1-双层和 A2-单层。计算结果表明，与远端轴突 (DA) 相比，钠通道带 (SOCB) 对刺激参数的调制不太敏感，DA 刺激阈值对 RGC 之间的生理差异不太敏感。因此，在 RGC 远端轴突直径的范围内，短脉冲对称双相波形可以增强 SOCB 和 DA 之间的刺激阈值差异。适当设计的波形可以避免 RGC 的轴突激活，这意味着视野中不希望的撞击会随之减少。计算结果表明，与远端轴突 (DA) 相比，钠通道带 (SOCB) 对刺激参数的调制不太敏感，DA 刺激阈值对 RGC 之间的生理差异不太敏感。因此，在 RGC 远端轴突直径的范围内，短脉冲对称双相波形可以增强 SOCB 和 DA 之间的刺激阈值差异。适当设计的波形可以避免 RGC 的轴突激活，这意味着视野中不希望的撞击会随之减少。计算结果表明，与远端轴突 (DA) 相比，钠通道带 (SOCB) 对刺激参数的调制不太敏感，DA 刺激阈值对 RGC 之间的生理差异不太敏感。因此，在 RGC 远端轴突直径的范围内，短脉冲对称双相波形可以增强 SOCB 和 DA 之间的刺激阈值差异。适当设计的波形可以避免 RGC 的轴突激活，这意味着视野中不希望的撞击会随之减少。短脉冲对称双相波形可以增强 SOCB 和 DA 之间的刺激阈值差异。适当设计的波形可以避免 RGC 的轴突激活，这意味着视野中不希望的撞击会随之减少。短脉冲对称双相波形可以增强 SOCB 和 DA 之间的刺激阈值差异。适当设计的波形可以避免 RGC 的轴突激活，这意味着视野中不希望的撞击会随之减少。