Experimental and Clinical Investigations of Retinal Stimulation

描述(由申请人提供)： 为盲人设计的视网膜假体已经显示出令人鼓舞的结果。植入设备的盲人患者在视觉指导任务中的行动能力和表现都有所改善。对于许多植入物患者来说，感知复杂形状的能力一直很困难。最近的心理物理学测试表明，许多单电极的知觉都被拉长了，超出了只有电极附近的视网膜被激活时的预期。这些结果，再加上体外视网膜的钙成像实验，表明轴突刺激比之前认为的更广泛。轴突刺激可能导致延长的感觉，不仅由电极下的视网膜神经节细胞产生，也由电极附近的视网膜神经节细胞产生，但其轴突通过电极下方。一系列研究发现，长时间的刺激可能选择性地针对视网膜内神经元，避免轴突的激活。支持这一建议的初步数据显示，20赫兹正弦波刺激在体外大鼠视网膜和植入视网膜假体的人身上引发了焦点反应。体内数据是使用一种新型的腺相关病毒载体记录的，该载体转导视网膜神经节细胞，使细胞表达细胞内钙指示剂GCaMP。初步结果表明，体外视网膜是一种很好的人类感知模型。拟议的生物工程研究伙伴关系将彻底调查体外视网膜的预测能力，因为它与人类的形状感知有关。将利用体外视网膜开发新的刺激方案。独特的视网膜成像技术将使人们能够前所未有地测量视网膜电刺激反应的空间范围。来自单个细胞的电生理记录将补充和验证成像数据。将测量对单电极和多电极刺激的响应。有希望的刺激将在植入视网膜的人类身上进行测试。因此，拟议研究的意义是双重的。首先，我们将通过确定最佳刺激方案来促进视网膜植入物患者的形状感知。其次，更广泛地说，我们将建立体外视网膜作为工具，为未来有望实现更高视力的植入物的设计提供信息。

DESCRIPTION (provided by applicant): Retinal prostheses for the blind have shown encouraging results. Blind patients implanted with devices have improved mobility and better performance in visually guided tasks. The ability to perceive complex shapes has been difficult for manyh implant patients. Recent psychophysics testing has shown that many single- electrode percepts are elongated, extending beyond what would be expected if only the retina near the electrode were activated. These results, coupled with calcium imaging experiments in in vitro retina, suggest more extensive axonal stimulation than previously believed. Axonal stimulation may result in elongated perceptions created not only by the retinal ganglion cells under the electrode, but also by the retinal ganglion cells distl to the electrode, but whose axons pass under the electrode. A series of studies have found that long-duration stimuli may target selectively inner retina neurons and avoid activation of axons. Preliminary data in support of this proposal shows that 20-Hz sine wave stimulation elicited a focal response in in vitro rat retina and in a human with a retinal prosthesis implant. The in vito data was recorded using a novel adeno-associated viral vector that transduces retinal ganglion cells such that the cells express an intracellular calcium indicator, GCaMP. The preliminary results suggest that in vitro retina is an excellent model for human perception. The proposed Bioengineering Research Partnership will thoroughly investigate the predictive power of in vitro retina as it relates to shape perception in humans. Novel stimulus protocols will be developed using in vitro retina. Unique retinal imaging techniques will allow unprecedented measurements of the spatial extent of electrically elicited responses from the retina. Electrophysiolgical recordings from single cells will complement and validate the imaging data. Responses to single and multi-electrode stimulation will be measured. Promising stimuli will be tested in humans with retinal implants. The significance of the proposed research is thus two-fold. First, we will advance shape perception in patients with retinal implants, by identifying optimal stimulus protocols. Secondly, and more broadly, we will establish in vitro retina as tool to infor the design of future implants that promise higher acuity vision.