Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Sci Rep. 2016 Dec 8;6:38505. doi: 10.1038/srep38505.
Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual information, is a potentially better alternative to electrical stimulation widely used in current retinal prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no subretinal electrical or chemical stimulation study has stimulated the OFF and ON pathways differentially through inner retinal activation. Here, we demonstrate the feasibility of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way. We show that controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way for future development of a neurotransmitter-based subretinal prosthesis offering more naturalistic vision and better visual acuity than electrical prostheses.
用神经递质对视网膜进行亚视网膜刺激，这是一种将视觉信息传递的正常方式，是目前用于治疗光感受器退行性疾病致盲的视网膜假体中广泛使用的电刺激的潜在更好替代方法。然而，没有任何亚视网膜电或化学刺激研究通过内视网膜激活来区分刺激 OFF 和 ON 通路。在这里，我们通过生物模拟的方式证明了用谷氨酸（一种主要的神经递质化学物质）在视网膜的内核层中以不同的方式刺激视网膜神经节细胞（RGC）的可行性。我们表明，在离体野生型大鼠视网膜的亚表面以受控的脉冲方式递送电刺激谷氨酸，可在 OFF 和 ON RGC 中引发高度局部化的同时抑制和兴奋的尖峰率反应。我们还介绍了 RGC 对亚视网膜注射谷氨酸的反应的时空特征和治疗性刺激参数。我们的研究结果可能为基于神经递质的亚视网膜假体的未来发展铺平道路，这种假体提供的视觉效果比电假体更自然，视力更好。
