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）： 为了使视力恢复约15万名退伍军人，这是由于视网膜变性性疾病（例如黄斑变性或色素性色素炎）而盲目的，我们的小组和其他人正在积极开发一种视网膜假体 - 一种旨在通过电力刺激的视网膜神经元来恢复视力的设备，这些神经元已显示出大量用于生存的视网膜神经元。最近的临床试验提供了有力的证据，表明此类设备可以将高水平的视力（例如阅读）恢复到盲人。但是，临床结果仍然高度不一致，感知质量仍然有些粗糙。由于引起视觉的质量被认为是直接来自视网膜中引起的神经活动模式的，因此我们正在开发新的刺激方法，从而创造特定的活动模式。来自视网膜下植入物的电极位于双极细胞附近（在先前由光感受器占据的空间中）。虽然双极细胞被认为是下视网膜刺激的靶标，但对于这些神经元如何反应刺激以及刺激的不同参数是否改变了它们的反应，知之甚少。另外，抑制性无长血管细胞也紧密位置到刺激的电极，因此也可以通过刺激激活。据认为，无长血管的激活抑制了视网膜对进一步刺激的反应。 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区分。因此，我们可以直接测量双极或无结向细胞的激活水平，以不同类型的刺激。我们的实验室具有丰富的经验，进行了这类测量，并初步结果表明，不同类型的刺激波形可以极大地影响双极细胞反应。此外，重要的是要了解视网膜退化时是否对刺激保持敏感。因此，我们将研究视网膜神经元对RD10小鼠视网膜变性各个阶段刺激的反应性。这项研究的结果将为我们自己设备以及其他研究小组的设备的刺激方法提供信息，并将改善引起视力的质量。