Li Huakun, Weiss Connor E, Pandiyan Vimal Prabhu, Nanni Davide, Liu Teng, Kung Pei Wen, Tan Bingyao, Barathi Veluchamy Amutha, Schmetterer Leopold, Sabesan Ramkumar, Ling Tong
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
Department of Ophthalmology, University of Washington, Seattle, WA 98109, USA.
bioRxiv. 2025 Mar 25:2025.03.22.644466. doi: 10.1101/2025.03.22.644466.
Rod photoreceptors are essential for vision under dim light conditions. The onset of rod-mediated vision is marked by the isomerization of rhodopsin. Here we demonstrate that human and rodent rods undergo a minute and rapid contraction of their outer segments immediately upon photoisomerization. The contraction is explained as an electro-mechanical manifestation of the rod early receptor potential generated in the disk membranes, which is challenging to access in electrophysiology. The bleach-strength dependence of the contraction was accounted by a voltage-dependent membrane tension model, developed earlier to explain a similar behavior in cones. The optical imaging of light-evoked electrical activity in rodent rods was facilitated by an ultrahigh-resolution point-scan optical coherence tomography (OCT) system coupled with unsupervised learning, while in humans, an adaptive optics line-scan OCT facilitated high-speed recordings in individual rods. The non-invasive optical imaging of rhodopsin activation will have a significant impact on diagnostics and treatment of retinal disease, especially given the vulnerability of rods in inherited and age-related macular degeneration.
视杆光感受器对于在暗光条件下的视觉至关重要。视杆介导的视觉开始以视紫红质的异构化为标志。在这里,我们证明人类和啮齿动物的视杆在光异构化后立即会经历其外段微小而快速的收缩。这种收缩被解释为在盘膜中产生的视杆早期感受器电位的机电表现,而这在电生理学中很难获取。收缩对漂白强度的依赖性由先前开发的用于解释视锥细胞中类似行为的电压依赖性膜张力模型来解释。结合无监督学习的超高分辨率点扫描光学相干断层扫描(OCT)系统促进了对啮齿动物视杆中光诱发电活动的光学成像,而在人类中,自适应光学线扫描OCT有助于在单个视杆中进行高速记录。视紫红质激活的非侵入性光学成像将对视网膜疾病的诊断和治疗产生重大影响,特别是考虑到视杆在遗传性和年龄相关性黄斑变性中的易损性。