Towards improved efficacy of retinal prosthetics

提高视网膜假体的功效

• 批准号: 9032370
• 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: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9032370
• 关键词: Address; Blinded; Brain; Cells; Clinical; Conscious; Development; Device Designs; Devices; Effectiveness; Electric Stimulation; Electrodes; Elements; Goals; Implant; Interneurons; Knowledge; Light; Macular degeneration; Manufacturer Name; Measures; Mediating; Methods; Neurons; Pathway interactions; Patients; Pattern; Performance; Physiological; Positioning Attribute; Process; Property; Reading; Recruitment Activity; Reporting; Research; Resolution; Retina; Retinal; Retinal Degeneration; Retinitis Pigmentosa; Sales; Scheme; Shapes; Signal Transduction; Speed; Stimulus; Synapses; Testing; Veterans; Vision; Work; base; blind; cell type; compare effectiveness; density; ganglion cell; implantable device; improved; improved mobility; insight; neural circuit; neural patterning; public health relevance; relating to nervous system; research clinical testing; research study; response; retinal neuron; retinal prosthesis

 DESCRIPTION (provided by applicant): To restore sight to ~150,000 veterans (and others) that are blind as the result of retinal degenerative diseases (e.g. macular degeneration or retinitis pigmentosa), several worldwide groups are 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. Ongoing clinical testing provides strong evidence that such devices have the potential to restore high levels of vision to the blind e.g. they enable shape recognition, improved ambulation and even allow some limited reading. Recent regulatory approval allows commercial sale of two of these devices, making this approach a viable treatment option. Unfortunately however, clinical results have been inconsistent and the quality of elicited percepts still remains crude in most patients. Because the quality of elicited vision is thought to arise directly from the pattern of neural activity elicited in the retina, we study and compare the patterns of neural activity that arise from different forms of stimulation with the goal of developing more effective stimulation methods. Targeting bipolar cells (retinal interneurons) with electric stimulation is thought to generally be advantageous because it utilizes the surviving retinal circuitry to create neural activity that presumably is a closer match to normal (physiological) signaling patterns, and therefore, easier for the brain to interpret. While most existing devices are thought to target bipolar cells, the actual benefits of this approach have not been evaluated previously and will be the focus of the first aim. Retinal degeneration can alter the synaptic pathways that shape bipolar-mediated patterns and we will therefore also evaluate how efficacy changes during the course of degeneration. Additional work from our lab suggests that the fading of percepts reported during clinical use may be tied to a loss of sensitivity that arises in response to repetitive activation of the retinal network (i.e. from bipolar cell activatin). We have new preliminary results that show considerable variability in the amount of loss and suggest that some of the cell types thought to mediate conscious vision may be the ones most sensitive to repetitive stimulation. Our goal in Aim 2 is to determine the sensitivity of all key cll types and evaluate whether the loss in sensitivity can be mitigated by alternative (repetitive) stimulation schemes. The final aim will look at the effectiveness with which small electrodes create physio- logical signaling patterns. Our preliminary results suggest small electrodes are less effective in activating the network and we will study their effectiveness in both the healthy and degenerate retinas. To maximize the translational value of our work, all testing will be performed with a clone of one of the commercially available devices - the Alpha-IMS from Retina Implant, AG.

 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（和其他人）恢复视力，全球多个组织正在开发一种视网膜假体 - 一种旨在通过电刺激视网膜内部来恢复视力的装置大量的神经元已被证明能够在退化过程中幸存下来，这提供了强有力的证据，表明此类设备有可能使盲人恢复高水平的视力。不幸的是，最近的监管批准允许其中两种设备进行商业销售，这使得这种方法成为一种可行的治疗选择，但临床结果不一致，并且引发的感知质量仍然很粗糙。在大多数患者中，因为诱发视力的质量被认为是重要的。 直接由视网膜引起的神经活动模式产生，我们研究并比较 人们认为，通过不同形式的刺激产生的神经活动模式，以开发更有效的刺激方法来靶向双极细胞（视网膜中间神经元）通常是有利的，因为它利用幸存的视网膜电路来产生可能的神经活动。与正常（生理）信号模式更匹配，因此更容易被大脑解读。虽然大多数现有设备被认为是针对双极细胞，但这种方法的实际好处尚未体现。 先前已进行过评估，这将是第一个目标的重点。视网膜变性可以改变形成双极介导模式的突触通路，因此我们还将评估在变性过程中功效如何变化。临床使用过程中报告的感知的变化可能与视网膜网络重复激活（即双极细胞激活）引起的敏感性丧失有关。损失并表明一些被认为介导意识视觉的细胞类型可能是对重复刺激最敏感的细胞类型，我们在目标 2 中的目标是确定所有关键细胞类型的敏感性，并评估是否可以通过以下方法减轻敏感性的损失。最终目标是研究小电极创建生理信号模式的有效性，我们的初步结果表明小电极在激活网络方面效果较差，我们将研究它们在健康和健康人群中的有效性。视网膜退化。为了最大限度地提高我们工作的转化价值，所有测试都将使用一种市售设备的克隆来执行 - 来自 Retina Implant, AG 的 Alpha-IMS。