Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs.
Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs.
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发表时间：
1999-08
影响因子：
4.4
通讯作者：
A. Majji;M. Humayun;J. Weiland;Satoshi Suzuki;S. D'Anna;E. D. Juan
中科院分区：
文献类型：
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作者：
A. Majji;M. Humayun;J. Weiland;Satoshi Suzuki;S. D'Anna;E. D. Juan
通过多电极阵列对因光感受器丧失而失明的人的视网膜进行短期模式电刺激，已经表明走动视力和有限的字符识别是可能的。为了开发可提供有用视力的可植入视网膜假体，这些结果需要在长时间的视网膜电刺激中维持。作为实现这一目标的第一步，测试了生物相容性和将电惰性电极阵列手术植入视网膜表面的可行性。方法：将5 × 5电极阵列（硅胶基质中的25个铂盘形电极）使用视网膜钉植入4只视力正常的杂种犬的视网膜表面。术前、术后2周每隔1周、术后2个月每隔2周、术后2个月每隔1个月、之后每隔1个月进行一次彩色眼底照相、荧光素血管造影、视网膜电图和视觉诱发电位检查。植入后2个月处死一只犬，植入后3个月处死另一只犬。进行视网膜的组织学评价。其余两只犬在植入手术后继续随访超过6个月。结果所有动物均未发生视网膜脱离、感染或无法控制的眼内出血。在整个随访期间，视网膜钉和视网膜阵列仍然牢固地固定在视网膜上。仅在视网膜钉插入部位周围观察到视网膜色素上皮色素沉着过度。未见植入物纤维包裹或眼内炎症。视网膜电图的A波和B波振幅在术后第一周测试时被抑制，但在随后的1周内恢复，并且在整个术后期间与正常未手术的对侧眼没有统计学差异。在术后任何时间段，视觉诱发电位的N1和P1波振幅与正常对侧眼无显著差异。血管造影显示，整个视网膜，包括电极阵列下的区域保持良好的灌注。同样，组织学评价显示电极阵列下方的视网膜几乎完全保存。结论：在视网膜前侧植入电极阵列（即，最靠近神经节细胞层的一侧）是手术可行的，对下层视网膜的损伤微不足道。铂和硅胶阵列以及金属钉具有生物相容性。随着在视网膜表面长时间植入非电活性设备的成功，长期视网膜电刺激的效果现在已经准备好接受测试，作为开发供人类使用的原型视网膜假体的下一步。
PURPOSE Short-term pattern electrical stimulation of the retina via multielectrode arrays in humans blind from photoreceptor loss has shown that ambulatory vision and limited character recognition is possible. To develop an implantable retinal prosthesis that would provide useful vision, these results need to be sustained over a prolonged period of retinal electrical stimulation. As a first step toward this goal, the biocompatibility and the feasibility of surgically implanting an electrically inactive electrode array onto the retinal surface was tested. METHODS A 5 x 5 electrode array (25 platinum disc-shaped electrodes in a silicone matrix) was implanted onto the retinal surface using retinal tacks in each of the 4 mixed-breed sighted dogs. Color fundus photography, fluorescein angiography, electroretinography, and visual evoked potentials were obtained preoperatively, at 1-week intervals for 2 weeks postoperatively, then at 2-week intervals up to 2 months postoperatively, and thereafter at 1-month intervals. One dog was killed at 2 months after implantation and a second dog after 3 months of implantation. Histologic evaluation of the retinas was performed. The remaining two dogs continue to be followed beyond 6 months after the implantation surgery. RESULTS No retinal detachment, infection, or uncontrolled intraocular bleeding occurred in any of the animals. Retinal tacks and the retinal array remained firmly affixed to the retina throughout the follow-up period. Hyperpigmentation of the retinal pigment epithelium was observed only around the site of retinal tack insertion. No fibrous encapsulation of the implant or intraocular inflammation was visible. A- and b-wave amplitudes of the electroretinogram were depressed at the first postoperative week testing but recovered over the ensuing 1 week and were not statistically different from the normal unoperated fellow eye throughout the postoperative period. N1 and P1 wave amplitudes of the visual evoked potentials were not significantly different from the normal fellow eyes at any of the postoperative test intervals. Fluorescein angiography showed that the entire retina including the area under the electrode array remained well perfused. Similarly, histologic evaluation revealed near total preservation of the retina underlying the electrode array. CONCLUSIONS Implantation of an electrode array on the epiretinal side (i.e., side closest to the ganglion cell layer) is surgically feasible, with insignificant damage to the underlying retina. The platinum and silicone arrays as well as the metal tacks are biocompatible. With the success of implanting an electrically inactive device onto the retinal surface for prolonged periods, the effects of long-term retinal electrical stimulation are now ready to be tested as the next step toward developing a prototype retinal prosthesis for human use.