Computing Luminance and Contrast in Prosthetically Driven Retina

项目摘要 由感光细胞死亡引起的失明，如视网膜色素变性和黄斑变性 退化是当今世界上不可逆失明的主要原因之一。电 通过视网膜假体装置刺激备用视网膜回路有望恢复视力，但 到目前为止，取得的成果充其量也是有限的。我们对电刺激如何与 剩余的视网膜电路执行基本的视觉计算是差的。设计更有效的视网膜 我们需要更好地了解假体刺激是如何激活病变的 视网膜回路 研究视网膜下刺激如何激活视网膜回路的两个主要挑战是：1） 缺乏测量双极细胞电激活的技术，以及2）对 视网膜退化如何改变视觉处理回路在这里，我们使用一种新的方法。通过 离体记录双极细胞的突触输出，我们可以直接读出相关的双极细胞活性， 这是视网膜下假体刺激的第一阶段。通过使用一种新的视网膜修复技术， 纳米线检测器阵列，以高的时间和空间精度模拟光输入到双极单元， 我们可以确定在退化过程中，诸如对比度之类的基本计算是如何改变的。 这一建议的结果将是重大的，并将：1。确定最佳刺激 用假肢恢复视力的策略2.）揭示基本的生理机制，决定 备用视网膜如何响应电刺激，以及3.）确定假肢如何 患病视网膜中的基本计算电路，以从空间中提取时间对比度信息， 电刺激的时间模式。这些实验将产生必要的洞察力， 早期视觉计算的基本机制和指导策略，以改善设计 以及视网膜修复装置的制作。这项工作的长期目标是改进 用于视力恢复的视网膜修复术，最终改善广大患者的生活质量 人口

PROJECT SUMMARY Blindness caused by photoreceptor death, such as in Retinitis Pigmentosa and Macular Degeneration, is among the leading causes of irreversible blindness in the world today. Electrical stimulation of spared retinal circuitry by retinal prosthetic devices holds promise for restoring vision, but results so far have been modest at best. Our understanding of how electrical stimulation engages the remaining retinal circuitry to perform basic visual computation is poor. To design more effective retinal prosthetic devices, we need to better understand how prosthetic stimulation activates the diseased retinal circuitry. Two major challenges to studying how sub-retina stimulation activates retinal circuitry are: 1) the lack of techniques to measure electrical activation of bipolar cells, and 2) an incomplete understanding of how retinal degeneration changes visual processing circuits. Here we use a new approach. By recording synaptic output of bipolar cells ex vivo, we can directly readout relevant bipolar cell activity, which is the first stage in sub-retinal prosthetic stimulation. By using a new retinal prosthetic technology, the nanowire detector array, to mimic light input to bipolar cells with high temporal and spatial precision, we can determine how basic computations such as contrast are altered during degeneration. The results from this proposal will be significant and will: 1.) Determine optimal stimulation strategies to restore vision with prosthetics 2.) Uncover basic physiological mechanisms that determine how spared retina responds to electrical stimulation, and 3.) Determine how prosthetics can engage basic computational circuitry in diseased retina to extract temporal contrast information from spatio- temporal patterns of electrical stimulation. These experiments will produce needed insight on the fundamental mechanisms underlying early visual computation and guide strategies to improve the design and execution of retinal prosthetic devices. The long-term goal of this work is to improve the design of retinal prosthetics for vision restoration, ultimately improving the quality of life for a broad patient population.