Feasibility of an Optogenetic Prosthesis for the Primate Eye

描述(申请人提供)：视网膜外部的光感受器和视网膜色素上皮(RPE)细胞非常容易受到退行性眼病的影响，但光遗传学的最新进展提供了在失去光感受器功能后恢复视力的可能性。这种方法已经在老鼠身上得到了演示。该项目将部署一个猴子模型，以探索通过使用光遗传学方法使视网膜神经节细胞对光敏感来绕过退化的光感受器的视网膜假体的可行性。猴子的模型是必要的，因为猴子有一个中心凹和人类一样的视觉感知。为了建立猴子视网膜变性的模型，我们将使用光毒性来选择性地破坏暴露在强光下的局部视网膜区域的光感受器。然后我们将尝试 通过玻璃体内注射设计用于表达通道视紫红质的病毒载体来转导神经节细胞以恢复光敏感性。我们将用两种方法评估光暴露破坏光感受器功能的效果和光遗传假体恢复功能的效果。首先，我们将使用基因编码的钙指示器测量神经节细胞的光反应，该指示器通过自适应光学成像在活着的眼睛中。该方法将允许我们在同一只猴子身上重复数周追踪神经节细胞的功能。第二，我们将通过视觉心理物理任务来测量光遗传假体的视觉效果。如果这些实验成功，它们将阐明应用于灵长类中心凹的光遗传假体的光敏性、动态范围和信息容量。

DESCRIPTION (provided by applicant): 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. Ths 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 vira 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.