Jonnal Ravi S
Department of Ophthalmology and Vision Science, University of California, Davis, CA, USA.
Ann Transl Med. 2021 Aug;9(15):1270. doi: 10.21037/atm-20-6440.
The past few years have witnessed rapid development of the optoretinogram-a noninvasive, optical measurement of neural function in the retina, and especially the photoreceptors (Ph). While its recent development has been rapid, it represents the culmination of hundreds of experiments spanning decades. Early work showed measurable and reproducible changes in the optical properties of retinal explants and suspensions of Ph, and uncovered some of the biophysical and biochemical mechanisms underlying them. That work thus provided critical motivation for more recent work based on clinical imaging platforms, whose eventual goal is the improvement of ophthalmic care and streamlining the discovery of novel therapeutics. The first part of this review consists of a selective summary of the early work, and identifies four kinds of stimulus-evoked optical signals that have emerged from it: changes in light scattered from the membranous discs of the Ph's outer segment (OS), changes in light scattered by the front and back boundaries of the OS, rearrangement of scattering material in and near the OS, and changes in the OS length. In the past decade, all four of these signals have continued to be investigated using imaging systems already used in the clinic or intended for clinical and translational use. The second part of this review discusses these imaging modalities, their potential to detect and quantify the signals of interest, and other factors influencing their translational promise. Particular attention is paid to phase-sensitive optical coherence tomography (OCT) with adaptive optics (AO), a method in which both the amplitude and the phase of light reflected from individual Ph is monitored as visible stimuli are delivered to them. The record of the light's phase is decoded to reveal a reproducible pattern of deformation in the OS, while the amplitude reveals changes in scattering and structural rearrangements. The method has been demonstrated in a few labs and has been used to measure responses from both rods and cones. With the ability to detect responses to stimuli isomerizing less than 0.01% of photopigment, this technique may prove to be a quick, noninvasive, and objective way to measure subtle disease-related dysfunction at the cellular level, and thus to provide an entirely new and complementary biomarker for retinal disease and recovery.
在过去几年中，视网膜电图（一种对视网膜，尤其是光感受器（Ph）的神经功能进行无创光学测量的技术）得到了迅速发展。尽管其近期发展迅速，但它是数十年间数百次实验的成果。早期研究显示，视网膜外植体和光感受器悬浮液的光学特性发生了可测量且可重复的变化，并揭示了其背后的一些生物物理和生化机制。因此，这项工作为基于临床成像平台的近期研究提供了关键动力，其最终目标是改善眼科护理并简化新型疗法的发现过程。本综述的第一部分对早期研究进行了选择性总结，并确定了从中出现的四种刺激诱发光学信号：从光感受器外段（OS）的膜盘散射的光的变化、OS前后边界散射的光的变化、OS内部及附近散射物质的重新排列以及OS长度的变化。在过去十年中，所有这四种信号都一直在使用已用于临床或打算用于临床及转化用途的成像系统进行研究。本综述的第二部分讨论了这些成像方式、它们检测和量化感兴趣信号的潜力以及影响其转化前景的其他因素。特别关注了带有自适应光学（AO）的相敏光学相干断层扫描（OCT），在这种方法中，当向单个光感受器施加可见刺激时，会监测从它们反射的光的幅度和相位。光的相位记录被解码以揭示OS中可重复的变形模式，而幅度则揭示散射和结构重排的变化。该方法已在一些实验室得到验证，并已用于测量视杆细胞和视锥细胞的反应。由于能够检测对光色素异构化少于0.01%的刺激的反应，这项技术可能被证明是一种在细胞水平测量与疾病相关的细微功能障碍的快速、无创且客观的方法，从而为视网膜疾病和恢复提供一种全新的补充生物标志物。
