Biology subjects

Schmetterer, L.

Publications and source records attributed to Schmetterer, L..

5 recordsLinked to original sources

bioRxiv2025

Optoretinography reveals rapid rod photoreceptor movement upon photoisomerization

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 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 coupled with unsupervised learning, while in humans, an adaptive optics line-scan OCT facilitated high-speed recordings in individual rods. The non-invasive in vivo 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.

bioengineering↗

bioRxiv2024

Interactions between high-intensity light and unrestricted vision in the drive for hyperopia

PURPOSETo evaluate the impact of optical versus illuminance factors and their duration-dependency on lens-induced hyperopia (LIH) in chick eyes. METHODSHyperopia was induced in one eye in chicks (10 groups, n=126) from day 1 (D1) post-hatching until D8 using +10 D lenses with fellow eyes as controls. One group (LIH) served as the control without any interventions. Remaining groups were exposed to 2, 4 or 6 hours of unrestricted vision (UnV), high intensity light (HL), or both (HL +UnV). Ocular axial length (AL), refractive error, and choroidal thickness were measured on days 1, 4, and 8. Inter-ocular difference (IOD = experimental - contralateral eye) {+/-} SEM was used to express outcome measures. RESULTSBy D8, LIH decreased AL (-0.42{+/-}0.03 mm) and produced hyperopic refraction (+3.48{+/-}0.32 D) and choroidal thickening (+85.81{+/-}35.23 {micro}m) in the LIH group (all, P<0.001). Exposure to UnV reduced LIH (i.e., hyperopic refraction, axial shortening, and choroidal thickening) in a duration-dependent manner, whereas HL potentiated the development of LIH in a duration-dependent manner. When combined, UnV overpowered HL, with resultant impact on refraction and AL being close to UnV alone, except after 6 hours, when HL+UnV induced shorter AL compared to UnV alone (P=0.03). CONCLUSIONDaily exposure to HL, UnV, and HL+UnV altered LIH in a duration-dependent manner with UnV and LIH producing competing signals. The signal generated by UnV was generally stronger than HL in combined exposure, yet longer durations of HL affected the drive for emmetropization in eyes with UnV.

developmental biology↗

bioRxiv2023

Automated, unbiased optoretinography reveals comprehensive nanoscopic dynamics of the outer retina in rodents

Phototransduction involves changes in concentration of ions and other solutes within photoreceptors and in subretinal space, which affect osmotic pressure and the associated water flow. Corresponding expansion and contraction of cellular layers can be imaged using optoretinography (ORG), based on phase-resolved optical coherence tomography (OCT). Until now, ORG could reliably detect only photoisomerization and phototransduction in photoreceptors, primarily in cones under very bright stimuli. By employing a novel subpixel bulk motion correction algorithm, which enabled imaging of the nanometer-scale tissue dynamics during minute-long recordings, and unsupervised learning of spatiotemporal patterns, we discovered optical signatures of the other retinal structures response to visual stimuli. These include inner and outer segments of rod photoreceptors, retinal pigment epithelium, and subretinal space in general. High sensitivity of our technique enabled detection of the retinal responses to very dim stimuli: down to 0.01% bleach level, corresponding to natural levels of scotopic illumination. We also demonstrated that with a single flash, the optoretinogram can map retinal responses across a 12{degrees}field of view, potentially replacing multifocal electroretinography, with its long acquisition time and low spatial resolution. This new technique expands the diagnostic capabilities and practical applicability of optoretinography, providing a more complete replacement of electroretinography, while combining structural and functional retinal imaging in the same OCT machine.

bioengineering↗

bioRxiv2022

Shot-noise limited phase-sensitive imaging of moving samples by phase-restoring subpixel motion correction in Fourier-domain optical coherence tomography

Phase-sensitive Fourier-domain optical coherence tomography (FD-OCT) enables in-vivo, label- free imaging of cellular movements with detection sensitivity down to the nanometer scale, and it is widely employed in emerging functional imaging modalities, such as optoretinography (ORG), Doppler OCT, and optical coherence elastography. However, when imaging tissue dynamics in vivo, tissue movement or bulk motion introduces decorrelation noise that compromises motion detection performance, particularly in terms of sensitivity and accuracy. Here, we demonstrate that the motion-related decorrelation noise in FD-OCT can be accurately corrected by restoring the initial sampling points using our proposed Phase-Restoring Subpixel Image Registration (PRESIR) method. Derived from a general FD-OCT model, the PRESIR method enables translational shifting of complex-valued OCT images over arbitrary displacements with subpixel precision, while accurately restoring phase components. Unlike conventional approaches that shift OCT images either in the spatial domain at the pixel level or in the spatial frequency domain for subpixel correction, our method reconstructs OCT images by correcting axial displacement in the spectral domain (k domain) and lateral displacement in the spatial frequency domain. We validated the PRESIR method through simulations, phantom experiments, and in-vivo optoretinography in both rodents and human subjects. Our approach significantly reduced decorrelation noise during the imaging of moving samples, achieving phase sensitivity close to the fundamental limit determined by the signal-to-noise ratio (SNR).

bioengineering↗

bioRxiv2019

Effect of Changing Heart Rate on the Ocular Pulse and Dynamic Biomechanical Behavior of the Optic Nerve Head

PurposeTo study the effect of changing heart rate on the ocular pulse and the dynamic biomechanical behaviour of the optic nerve head (ONH) using a comprehensive mathematical model.\n\nMethodsIn a finite element model of a healthy eye, a biphasic choroid consisted of a solid phase with connective tissues and a fluid phase with blood, and the lamina cribrosa (LC) was viscoelastic as characterized by a stress-relaxation test. We applied arterial pressures at 18 ocular entry sites (posterior ciliary arteries) and venous pressures at four exit sites (vortex veins). In the model, the heart rate was varied from 60 bpm to 120 bpm (increment: 20 bpm). We assessed the ocular pulse amplitude (OPA), pulse volume, ONH deformations and the dynamic modulus of the LC at different heart rates.\n\nResultsWith an increasing heart rate, the OPA decreased by 0.04 mmHg for every 10 bpm increase in heart rate. The ocular pulse volume decreased linearly by 0.13 {micro}L for every 10 bpm increase in heart rate. The storage modulus and the loss modulus of the LC increased by 0.014 MPa and 0.04 MPa, respectively, for every 10 bpm increase in heart rate.\n\nconclusionsIn our model, the OPA, pulse volume, and ONH deformations decreased with an increasing heart rate, while the LC became stiffer. The effects of blood pressure / heart rate changes on ONH stiffening may be of interest for glaucoma pathology.\n\nSupportSingapore Ministry of Education, Academic Research Fund, Tier 2 (R-397-000-280-112).\n\nCommercial relationshipNone

bioengineering↗