Optoretinography reveals rapid rod photoreceptor movement upon rhodopsin activation

TL;DR

A new imaging technique shows rapid rod photoreceptor changes in response to light, offering a non-invasive way to study retinal diseases.

Contribution

The study introduces optoretinography to capture rapid rod photoreceptor movement during rhodopsin activation in vivo.

Findings

Rod photoreceptors contract rapidly in their outer segments upon rhodopsin activation.

Optoretinography enables non-invasive imaging of rod dysfunction in retinal diseases.

The contraction is linked to the rod's early receptor potential, previously hard to measure.

Abstract

Rod photoreceptors are essential for vision under dim light conditions and are highly vulnerable in retinal degenerative diseases. Here, we demonstrate that both human and rodent rods undergo a minute and rapid contraction of their outer segments upon photoisomerization, the first step of phototransduction. The contraction is explained as an electromechanical manifestation of the rod early receptor potential generated in the disk membranes, which is challenging to access in electrophysiology. The in vivo optical imaging of light-evoked electrical activity in rodent rods was facilitated by an ultrahigh-resolution point-scan optical coherence tomography (OCT) system, combined with an unsupervised learning approach to separate the light-evoked response of the rod outer segment tips from the retinal pigment epithelium-Bruch’s membrane complex. In humans, an adaptive optics line-scan OCT facilitated high-speed recordings in rods. The non-invasive in vivo optical imaging of rhodopsin activation extends the diagnostic capability of optoretinography, and may facilitate personalized, objective assessment of rod dysfunction and visual cycle impairment in inherited and age-related macular degeneration.

Optoretinography reveals rapid deformations in human and rodent rod photoreceptors associated with rhodopsin activation, paving the way for label-free imaging of rod dysfunction and visual cycle impairment in retinal diseases.

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