Bartuzel, M. M. | Search bioRxiv

bioRxiv2026

Dark adaptation of cone photoreceptor responses is revealed by optoretinography

Dark adaptation is the essential process that restores visual sensitivity following exposure to bright light, yet the underlying mechanisms remain incompletely understood. Here, we propose a method for assessing dark adaptation in cones using optoretinography (ORG) based on adaptive optics optical coherence tomography (AO-OCT). ORG quantifies cone functional response by monitoring nano-scale changes in the cones outer segment occurring over hundreds of milliseconds after visible stimulation. This method consists of sequential measurements of stimulus-evoked cone responses over the course of minutes of dark adaptation. Each response captures optical path length changes in single photoreceptor outer segments over milliseconds during a multi-minute recovery period following a strong photopigment bleach. We parameterized cone ORG responses and proposed an exponential model linking ORG dynamics to pigment regeneration. Parameters of the ORG response exhibited exponential decay behavior during dark adaptation, and were thus fit with exponential functions and quantified by the resulting decay parameter{tau} . Parameters capturing the amplitude of the ORG responses recovered more slowly than those capturing temporal dynamics of the responses. This difference is consistent with distinct contributions from photopigment regeneration and downstream phototransduction processes. Recovery speed varied by two-to threefold among three normal subjects, suggesting substantial inter-subject physiological diversity. Processes within the cone, including pigment regeneration, are thought to underlie the gains in photopic visual sensitivity that occur in the dark. These findings highlight ORG as an objective and sensitive assay of those cellular mechanisms. While the ORG itself has shown promise as a biomarker of the health of the photoreceptor response to light, the results of this study show that it may also be useful for probing the health of the intra- and intercellular homeostatic mechanisms that support it.

neuroscience↗

bioRxiv2025

Subretinal aspects of the optoretinographic response

1Water movement in the living human retina and its regulation are important components of the tissues structural integrity, optical properties, and homeostasis. In the outer retina there is a continuous flow of water from the subretinal space, through the retinal pigmented epithelium, and into the choroid. This flow is disrupted acutely in disorders such as retinal detachment and central serous retinopathy, and is also known to reduce dramatically with age and age-related macular degeneration. Optoretiongraphy is an emerging technique for measuring neural function in the retina by monitoring nanometer-scale deformations of the membranes of photoreceptors. These deformations have been hypothetically attributed, in part, to osmotic shifts that cause water to move into and out of the photoreceptor outer segment after light stimulation. In the present work, we describe a method for measuring changes in the lengths of the cone outer segment and subretinal space in parallel and results showing that light stimuli change the volume of the subretinal space. These results are consistent with earlier ex vivo measurements of its light-induced hydration. The magnitude of the latter changes depend on the rate of water clearance from the subretinal space, and thus may serve as an indicator of the health of the water transport system. In addition, they may help us understand the mechanisms underlying the photoreceptor optoretinogram. These findings add to a growing understanding of the ways in which light exposure leads to transient reconfigurations of the outer retinal layers lasting milliseconds to hours.

neuroscience↗