Biology subjects

Paques, M.

Publications and source records attributed to Paques, M..

6 recordsLinked to original sources

bioRxiv2026

Biomechanical stress in the retinal pigment epithelium surrounding laser scars in humans

Purpose : The wound response of an epithelium comprises tissue-scale activation of stress fibers whose contraction regionally reconfigures the epithelium and drives closure of the wound. Recent in vitro studies have shown that similar biomechanical processes can paradoxically lead to enlargement of epithelial holes. In patients having undergone laser photocoagulation of the retinal pigment epithelium (RPE), laser scars may expand over years. Here, to document the implication of epithelial biomechanics in the enlargement of laser scars we analyzed the dynamic changes affecting the RPE around scars in patients and performed confocal microscopy on a RPE flat-mount from a donor eye. Methods: We analyzed the image files of five patients (age 61 to 85 years) showing enlargement of laser scars in the RPE (follow-up, 13 to 60 months). In three of them, prospective imaging was performed using transscleral illumination adaptive optics ophthalmoscopy (AOO), an imaging technology enabling visualization of RPE cells. Time-lapse sequences were analyzed to track dynamic processes in the RPE surrounding scars. A flat-mounted phalloidin-labeled RPE from a human donor eye with a history of scatter photocoagulation was examined by confocal microscopy to document the distribution of stress fibers and cell metrics. Results: Time-lapse sequences showed that enlargement of laser scars was accompanied by the displacement of microscopic features in margins of atrophy. AOO imaging suggested locally coordinated displacement of mosaic of darks spots, with a generally radial or tangent direction relative to the edges of scars. Such movements were detected up to several hundred microns from the edges of scars. On the histology sample, elongated RPE cells with stress fibers forming actin cables were found along edges of scars, which formed fascicles between adjacent scars. Conclusion: Enlargement of RPE scars may be accompanied by long-lasting, largescale changes in the distribution of microscopic features in the margins of lesions. In particular, transscleral illumination AOO showed coordinated displacement of a mosaic similar to the one described for the RPE. The finding by histology of RPE cell with a tractional phenotype along edges further suggests that epithelial biomechanics contribute to such movements and may hence contribute to scar enlargement.

pathology↗

bioRxiv2025

The novel phenomenon of inter-retinal coupling predicts cortical neurovascular responses in health and disease

It has recently been discovered that physiological crosstalk exists between human retinas. Accordingly, visual stimulation of one retina elicited a neurovascular coupling (NVC) response of the contralateral retina in about 30% of individuals. The functional significance of this feature in health and disease remains unknown. Here, we asked the question whether inter-retina crosstalk predicts the nature of neurovascular coupling in the brain. To test this hypothesis, we assessed BOLD fMRI (blood-oxygen-level-dependent functional magnetic resonance imaging signal) in healthy individuals and a disease model of neurovascular coupling, type 1 diabetes. We used three visual paradigms: a Threshold speed and Sub-maximum speed discrimination tasks, and flicker stimulation. The presence or absence of inter-retinal coupling was predictive of the time course of the cortical hemodynamic response, either during the initial or late phases. The presence of interocular coupling predicted larger BOLD responses. Diabetic patients with interocular coupling showed a very similar profile to the healthy group. In sum, we identified a direct relationship between interocular physiological coupling and cortical hemodynamic responses, suggesting that this NVC response may serve as a disease biomarker in diabetes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/684136v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@74ae56org.highwire.dtl.DTLVardef@61a2ccorg.highwire.dtl.DTLVardef@7349dorg.highwire.dtl.DTLVardef@10f61b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Adaptive Optics Rolling Slit Ophthalmoscope: Combining cellular-resolution, high-speed and large field-of-view in a multimodal retinal imager

Label-free optical imaging systems capable of monitoring dynamic biological processes over a large field-of-view (FOV) are essential for advancing our understanding of retinal and neurovascular health. However, existing imaging modalities often involve trade-offs between spatial resolution, contrast, FOV, and frame rate. In this study, we present the Adaptive Optics Rolling Slit Ophthalmoscope (AO-RSO), a novel imaging system that integrates the high-speed, wide-FOV capabilities of camera-based systems with the enhanced contrast and multimodal functionality of point-scanning techniques--without compromising resolution or speed. The AO-RSO utilizes line illumination synchronized with the rolling shutter of a high-speed sCMOS camera, enabling precise and dynamic spatial selection of detected photons: back-scattered photons for near-confocal bright-field imaging and forward-scattered photons for phase-contrast imaging of translucent retinal features. This system successfully visualizes diverse retinal structures, including cone and rod photoreceptors, nerve fiber bundles, red blood cells, vessel walls, and ganglion cells, across a wide retinal area (4.5{degrees}x 2.5{degrees}). With a large FOV and frame rates up to 200 Hz, the AO-RSO enables the quantification of blood flow, tracking of red blood cells within hundreds of capillaries, and evaluation of thousands of photoreceptors in the living human retina. This capability opens new opportunities for functional neuronal imaging, neurovascular coupling studies, and the early detection of retinal and neurodegenerative diseases.

bioengineering↗

bioRxiv2024

Measuring flicker induced vasodilation at a high spatial and temporal resolution in the human retina.

Neurovascular coupling (NVC) is a crucial process in which blood flow is dynamically adjusted to meet the metabolic demands of active neurons. In this study, we introduce an innovative method for in-vivo imaging of retinal blood vessel dilation in response to visible light stimulation, offering insights into the functional regulation of retinal blood flow. Using high-resolution, high-speed phase contrast imaging, we continuously monitored retinal vessel dynamics in eight healthy subjects, capturing precise temporal and spatial changes in vessel size under both stimulated and baseline conditions. We have measured a significant vessel dilation of 5.2% {+/-} 1.6% (4.4 {micro}m {+/-} 1.3 {micro}m) during flicker-stimulation compared to a dilation of 2.5% {+/-} 1% (2.1 {micro}m {+/-} 0.9 {micro}m) without stimulation. The flexibility of our method also allowed for the exploration of various acquisition and stimulation settings, broadening possibilities for investigating neurovascular coupling in the retina. This work not only enhances our understanding of neurovascular coupling but also has the potential to identify new biomarkers for vision-impairing conditions and neurodegenerative diseases. SignificanceNeurovascular coupling is a fundamental mechanism of the brain which locally regulates blood flow in response to changes in neuronal activity. Here, we present a new imaging technique that enables measuring vasodilation in response to visible light stimulation of the neurons at high spatial and temporal resolution in the living human retina. Owing to the unprecedented measurement precision of the presented technique, we provide new insights into the inner working of functional blood flow regulation in the retina. Clinically, this method holds promise for vascular dysfunction early detection, which can improve diagnosis of retinal and neurodegenerative diseases, as well as assist the development of new targeted therapies.

neuroscience↗

bioRxiv2023

Foveal drusen increase fixation instability: fixational eye movements as biomarkers for pre-symptomatic AMD

PurposeThis study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic Age-related Macular Degeneration (AMD). MethodsWe recruited 7 young controls, 4 older controls and 16 presymptomatic AMD patients with foveal drusen from the Silversight Cohort. A high speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO. ResultsFEM were measured with high precision (RMS-S2S=0.0015{degrees} on human eyes) and small foveal drusen (median=60{micro}m) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient and ISOline Area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea. ConclusionsA novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

neuroscience↗

bioRxiv2021

A multiscale spatiotemporal model explains succession in the early infant gut microbiota as a switch from aerobic to anaerobic metabolism

The human intestinal microbiota starts to form immediately after birth, and is important for the health of the host. During the first days facultatively anaerobic bacterial species generally dominate, such as Enterobacteriaceae. These are succeeded by strictly anaerobic species, particularly Bifidobacterium species. An early transition to Bifidobacterium species is associated with health benefits: for example, Bifidobacterium species repress growth of pathogenic competitors and modulate the immune response. Succession to Bifidobacterium is thought to be due to consumption of intracolonic oxygen present in newborns by facultative anaerobes, including Enterobacteriaceae. To study if oxygen depletion suffices for the transition to Bifidobacterium species, here we introduce a multiscale mathematical model that considers metabolism, spatial bacterial population dynamics and cross-feeding. Using publicly available metabolic network data from the AGORA collection, the model simulates ab initio the competition of strictly and facultatively anaerobic species in a gut-like environment under the influence of lactose and oxygen. The model predicts that individual differences in intracolonic oxygen in newborn infants can explain the observed individual variation in succession to anaerobic species, in particular Bifidobacterium species. Bifidobacterium species become dominant in the model by using the bifid shunt, which allows Bifidobacterium to switch to sub-optimal yield metabolism with fast growth at high lactose concentrations as predicted here using flux-balance analysis. The computational model thus allows us to test the internal plausibility of hypotheses for bacterial colonization and succession in the infant colon. IMPORTANCEThe composition of the infant microbiota has a great impact on infant health, but its controlling factors are still incompletely understood. The frequently dominant anaerobic Bifidobacterium species benefit health, e.g., because they can keep harmful competitors under control and modulate the intestinal immune response. Controlling factors could include nutritional composition and intestinal mucus composition, as well as environmental factors, such as antibiotics. We introduce a modeling framework of a metabolically realistic intestinal microbial ecology in which hypothetical scenarios can be tested and compared. We present simulations that suggest that greater levels of intra-intestinal oxygenation more strongly delay the dominance of Bifidobacterium species, explaining the observed variety of microbial composition and demonstrating the use of the model for hypothesis generation. The framework allows us to test a variety of controlling factors, including intestinal mixing and transit time. Future versions will also include detailed modeling of oligosaccharide and mucin metabolism.

systems biology↗