Informing the Sub-Retinal Approach to Stimualation of the Retina.

告知视网膜下刺激视网膜的方法。

• 批准号: 8240901
• 负责人: Shelley Fried
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8240901
• 关键词: Affect; Age; Amacrine Cells; Blindness; Cells; Clinical; Clinical Trials; Control Animal; Device Designs; Devices; Disease; Effectiveness; Electric Stimulation; Electrodes; Electronics; Eye; Generations; Implant; Individual; Knowledge; Lead; Macular degeneration; Measurement; Measures; Methods; Modeling; Mus; Neurons; Patients; Pattern; Performance; Photoreceptors; Population; Positioning Attribute; Process; Property; Prosthesis; Rattus; Reading; Research; Retina; Retinal; Retinal Degeneration; Retinitis Pigmentosa; Shapes; Soldier; Sorting - Cell Movement; Staging; Stimulus; Testing; Veterans; Vision; Visual; blind; experience; ganglion cell; implantable device; improved; insight; neural patterning; patch clamp; relating to nervous system; response; retinal bipolar neuron; retinal neuron; retinal prosthesis; retinal stimulation; success; tool

DESCRIPTION (provided by applicant): To restore sight to ~150,000 veterans that are blind as the result of retinal degenerative diseases (e.g. macular degeneration or retinitis pigmentosa), our group and others are actively developing a retinal prosthetic - a device designed to restore vision by electrically stimulating inner retinal neurons, large numbers of which have been shown to survive the degeneration process. Recent clinical trials provide strong evidence that such devices can restore high levels of vision (e.g. reading) to the blind. However, clinical results are still highly inconsistent and percept quality remains somewhat crude. Because the quality of elicited vision is thought to arise directly from the pattern of neural activity elicited in the retina, we are developing new stimulation methods that create specific patterns of activity. Electrodes from the sub-retinal implant are positioned adjacent to bipolar cells (in the space previously occupied by the photoreceptors). While bipolar cells are thought to be the target of sub-retinal stimulation, little is known about how these neurons respond to stimulation, and, whether different parameters of stimulation alter their response. In addition, inhibitory amacrine cells are also closely situated to the stimulating electrodes and, as a result, may also be activated by stimulation. Activation of amacrine cells is thought to suppress the retinal response to further stimulation. Patch clamp measurements are a powerful tool for studying this kind of response as they allow two important components of the elicited response to be measured: (1) the excitatory (or inhibitory) input to ganglion cells can be measured directly (a measure of bipolar or amacrine cell activation), and (2) individual spikes can be measured in ganglion cells - pharmacological manipulation allows the spikes arising from bipolar cell activation to be distinguished. Thus, we can directly measure the activation levels of bipolar or amacrine cells to different types of stimulation. Our lab has much experience making these sorts of measurements and preliminary results suggest that different types of stimulus waveforms can greatly affect the bipolar cell response. In addition, it is important to understand whether bipolar cells remain responsive to stimulation as the retina degenerates. Therefore, we will study the responsiveness of retinal neurons to stimulation at various stages of retinal degeneration in the rd10 mouse. Findings from this study will inform the stimulation methods of our own device as well as by the devices of other research groups and will lead to improvements in the quality of elicited vision.

描述（由申请人提供）： 为了使约 150,000 名因视网膜退行性疾病（例如黄斑变性或色素性视网膜炎）而失明的退伍军人恢复视力，我们的团队和其他人正在积极开发视网膜假体 - 一种旨在通过电刺激视网膜内部神经元来恢复视力的装置，其中大量已被证明能够在退化过程中幸存下来。最近的临床试验提供了强有力的证据，表明此类设备可以使盲人恢复高水平的视力（例如阅读）。然而，临床结果仍然高度不一致，感知质量仍然有些粗糙。由于诱发视觉的质量被认为直接源自视网膜中诱发的神经活动模式，因此我们正在开发新的刺激方法来创建特定的活动模式。来自视网膜下植入物的电极位于双极细胞附近（在先前被光感受器占据的空间中）。虽然双极细胞被认为是视网膜下刺激的目标，但人们对这些神经元如何响应刺激以及不同的刺激参数是否会改变它们的反应知之甚少。此外，抑制性无长突细胞也靠近刺激电极，因此也可能被刺激激活。无长突细胞的激活被认为可以抑制视网膜对进一步刺激的反应。膜片钳测量是研究这种反应的有力工具，因为它们允许测量引发反应的两个重要组成部分：（1）可以直接测量神经节细胞的兴奋性（或抑制性）输入（双极或双极或抑制性输入的测量）无长突细胞激活），以及（2）可以在神经节细胞中测量单个尖峰 - 药理学操作可以区分双极细胞激活产生的尖峰。因此，我们可以直接测量双极细胞或无长突细胞对不同类型刺激的激活水平。我们的实验室在进行此类测量方面拥有丰富的经验，初步结果表明，不同类型的刺激波形可以极大地影响双极细胞的反应。此外，了解当视网膜退化时双极细胞是否仍然对刺激有反应也很重要。因此，我们将研究rd10小鼠视网膜变性各个阶段视网膜神经元对刺激的反应性。这项研究的结果将为我们自己的设备以及其他研究小组的设备的刺激方法提供信息，并将导致引出视觉质量的提高。