Advanced adaptive optics instrumentation for ophthalmic imaging and function testing: the single cell approach to visual function and dysfunction

体内神经视网膜成像的关键发展增加了我们对视觉如何工作以及疾病如何破坏我们的视觉能力的理解。例如，将低相干干涉测量的概念结合到成像中为光学相干断层扫描（OCT）铺平了道路，当应用于眼睛时，光学相干断层扫描能够以接近细胞的分辨率提供眼部结构的图像。商业OCT系统已经彻底改变了临床实践。自适应光学的应用，以克服眼睛的缺陷，现在提供了成像系统足够的访问，以可视化活的人类视网膜中的单个细胞。特别是，自适应光学扫描激光检眼镜（AOSLO）为临床医生和视觉科学家提供了无与伦比的分辨率，可以在体内细胞水平上探测视觉的基础。通过结合基于图像的眼睛跟踪和快速光开关控制，AOSLO还可以用于将光传递到视网膜上的目标细胞，从而创造了将视网膜结构与视觉功能直接联系起来的独特可能性。该提案旨在设计一种基于AOSLO的微刺激器，可在临床环境中常规使用。在临床上，AOSLO将有助于更早地表征视网膜疾病进展，并在活体受试者的个体光感受器水平上监测药物干预。这种策略减少了对动物模型的需要，或者在视网膜疾病的新治疗的开发阶段中的低效、长期的组织学验证。除了临床应用外，细胞水平的活神经元组织访问打开了一扇大门，可以在以前无法进入的微观尺度上用心理物理方法研究视觉功能的基础知识。

Key developments in in vivo neuroretinal imaging have increased our understanding of how vision works and how diseases undermine our ability to see. For example, incorporating the concept of low-coherence interferometry to imaging paved the way for optical coherence tomography (OCT), which when applied to the eye is capable of delivering images of ocular structure with near-cellular resolution. Commercial OCT systems have revolutionized clinical practice. The application of adaptive optics to overcome the eye’s imperfections has now provided imaging systems sufficient access to visualize individual cells in the living human retina. In particular, the adaptive optics scanning laser ophthalmoscope (AOSLO) provides clinicians and vision scientists with unparalleled resolution to probe the basis of vision at the cellular level in vivo. By incorporating image-based eye tracking and fast light switching control, the AOSLO can also be used to deliver light to targeted cells on the retina, thereby creating the unique possibility to relate retinal structure to visual function directly. This proposal aims to design an AOSLO based micro-stimulator that can be routinely used in a clinical environment. In the clinic, the AOSLO will help characterize retinal disease progression earlier and monitor pharmaceutical intervention at the level of individual photoreceptors in living subjects. This strategy lessens the need of animal models or inefficient, protracted histological validation in the development phase of novel treatments for retinal diseases. In addition to clinical applications, cell-level access to living neuronal tissue opens the door to study the basics of visual function with psychophysical methods at a previously inaccessible microscopic scale.