Retinal prosthesis can restore partial vision in patients with retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Epiretinal prosthesis is one of three therapeutic approaches, which received regulatory approval several years ago. The thresholds of an epiretinal stimulation is partly determined by the size of the physical gap between the electrode and the retina after implantation. Precise positioning of epiretinal stimulating electrode array is still a challenging task. In this study, we demonstrate an approach to positioning epiretinal prostheses for an optimal response at the cortical output by monitoring both the impedance at the electrode-retina interface and the evoked-potential at the cortical level. We implanted a single-channel electrode on the epiretinal surface in adult rats, acutely, guided by both the impedance at the electrode-retina interface and by electrically evoked potentials (EEPs) in the visual cortex during retinal stimulation. We observe that impedance monotonously increases with decreasing electrode-retina distance, but that the strongest cortical responses were achieved at intermediate impedance levels. When the electrode penetrates the retina, the impedance keeps increasing. The effect of stimulation on the retina changes from epiretinal paradigm to intra-retinal paradigm and a decrease in cortical activation is observed. It is found that high impedance is not always favorable to elicit best cortical responses. Histopathological results showed that the electrode was placed at the intra-retinal space at high impedance value. These results show that monitoring impedance at the electrode-retina interface is necessary but not sufficient in obtaining strong evoked-potentials at the cortical level. Monitoring the cortical EEPs together with the impedance can improve the safety of implantation as well as efficacy of stimulation in the next generation of retinal implants.

中文翻译：

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在大鼠视网膜上刺激下监测皮质反应和电极-视网膜阻抗

视网膜假体可以恢复视网膜色素变性和年龄相关性黄斑变性等视网膜退行性疾病患者的部分视力。视网膜前假体是几年前获得监管部门批准的三种治疗方法之一。视网膜前刺激的阈值部分取决于植入后电极和视网膜之间的物理间隙的大小。视网膜前刺激电极阵列的精确定位仍然是一项具有挑战性的任务。在这项研究中，我们展示了一种通过监测电极-视网膜界面的阻抗和皮层水平的诱发电位来定位视网膜前假体以在皮层输出处获得最佳响应的方法。我们在成年大鼠的视网膜前表面植入了一个单通道电极，急性，由电极-视网膜界面的阻抗和视网膜刺激期间视觉皮层中的电诱发电位 (EEP) 引导。我们观察到阻抗随着电极-视网膜距离的减小而单调增加，但最强的皮质反应是在中等阻抗水平下实现的。当电极穿透视网膜时，阻抗不断增加。刺激对视网膜的影响从视网膜前范式变为视网膜内范式，并观察到皮质激活的减少。发现高阻抗并不总是有利于引发最佳皮质反应。组织病理学结果显示电极以高阻抗值置于视网膜内空间。这些结果表明，监测电极-视网膜界面的阻抗是必要的，但不足以在皮质水平获得强诱发电位。监测皮质 EEP 和阻抗可以提高植入的安全性以及下一代视网膜植入物的刺激效果。