Experimental and Clinical Investigations of Retinal Stimulation

描述（由申请人提供）： 盲人视网膜假体显示出令人鼓舞的结果。 植入设备的盲人患者在视觉引导任务中的移动性和表现有所改善。 对于许多植入患者来说，感知复杂形状的能力是困难的。 最近的心理物理学测试表明，许多单电极感知被拉长，超出了只有电极附近的视网膜被激活时的预期。 这些结果，再加上钙成像实验在体外视网膜，表明更广泛的轴突刺激比以前认为的。 轴突刺激可以导致不仅由电极下的视网膜神经节细胞产生的伸长感知，而且由远离电极但其轴突在电极下通过的视网膜神经节细胞产生的伸长感知。 一系列的研究发现，长时间的刺激可能选择性地靶向视网膜内层神经元，避免轴突的激活。 支持这一建议的初步数据表明，20赫兹正弦波刺激引起了在体外大鼠视网膜和人与视网膜假体植入局灶性反应。 使用一种新型腺相关病毒载体记录体内数据，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，离体视网膜是一个很好的模型，为人类的知觉。 拟议的生物工程研究伙伴关系将彻底研究体外视网膜的预测能力，因为它与人类的形状感知有关。 新的刺激协议将开发使用体外视网膜。 独特的视网膜成像技术将允许前所未有的测量空间范围的电引起的反应，从视网膜。 来自单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反应。 有希望的刺激将在植入视网膜的人类身上进行测试。 因此，拟议的研究具有双重意义。 首先，我们将通过确定最佳刺激方案来提高视网膜植入患者的形状感知。 其次，更广泛地说，我们将建立体外视网膜作为工具，为未来植入物的设计提供信息，以保证更高的视力。

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.