Feasibility of an Optogenetic Prosthesis for the Primate Eye

摘要 视网膜外部的光感受器和视网膜色素上皮(RPE)细胞 极易患退行性眼病，但光遗传学的最新进展提供了 光感受器功能丧失后恢复视力的可能性。这种方法具有 已经在老鼠身上演示过了。该项目将部署一个猴子模型来 探索绕过退化的光感受器的视网膜假体的可行性 通过使用光遗传方法使视网膜神经节细胞对光敏感。猴子 模型是必要的，因为猴子的中心凹和人类一样的视觉感知。至 建立猴视网膜变性模型，我们将利用光毒性选择性地 暴露在强光下后，破坏局部视网膜区域的光感受器。我们 然后尝试通过将神经节细胞转化为 玻璃体内注射旨在表达视紫红质通道的病毒载体。我们会 评价光照对光感受器功能的破坏作用 光遗传假体在恢复双眼功能中的作用 方法：研究方法。首先，我们将用遗传学方法测量神经节细胞的光反应 编码的钙指示器，通过自适应光学在活眼中成像。该方法将 允许我们在相同的时间内重复跟踪神经节细胞的功能 猴子。第二，我们将测量光遗传假体的视觉效果 完成视觉心理物理任务。如果这些实验成功，他们将澄清 光生生物的感光性、动态范围和信息能力 用于灵长类中心凹的假肢。

Abstract Photoreceptors and retinal pigment epithelium (RPE) cells in the outer retina are highly vulnerable to degenerative eye disease, but recent advances in optogenetics offer the possibility of restoring vision after loss of photoreceptor function. This approach has been demonstrated already in the mouse. This project will deploy a monkey model to explore the feasibility of a retinal prosthetic that bypasses degenerated photoreceptors by using optogenetic methods to make retinal ganglion cells light-sensitive. The monkey model is needed because the monkey has a fovea and human-like visual perception. To establish a monkey model of retinal degeneration, we will use phototoxicity to selectively destroy photoreceptors in localized retinal areas following exposure to bright light. We will then attempt to restore light sensitivity by transducing ganglion cells with an intravitreal injection of a viral vector designed to express channelrhodopsin. We will evaluate both the effectiveness of the light exposure in destroying photoreceptor function and the effectiveness of the optogenetic prosthesis in restoring function with two methods. First, we will measure the light responses of ganglion cells with a genetically encoded calcium indicator, imaged in the living eye with adaptive optics. The method will allow us to track ganglion cell function repeatedly over many weeks in the same monkey. Second, we will measure the visual effectiveness of the optogenetic prosthetic with visual psychophysical tasks. If these experiments are successful, they will clarify the photosensitivity, dynamic range, and information capacity of an optogenetic prosthetic applied to the primate fovea.