Biology subjects

Pardue, M. T.

Publications and source records attributed to Pardue, M. T..

7 recordsLinked to original sources

bioRxiv2026

Model of naturally occurring refractive error (NORE) in mice

PurposeAnimal models of myopia typically induce monocular refractive shifts via form deprivation (FD) or lens-induced myopia (LIM), modeling susceptibility to myopia, but with potentially limited applicability to childhood myopia. Here we describe a novel, genetically diverse mouse model of naturally occurring refractive error (NORE) with three distinct refractive phenotypes: hyperopic, myopic, and intermediate. MethodsC57BL/6J mice were mated to 129S2/SvPasCrl mice to create F1 or F2 offspring. Refractive errors in male and female F1 (N=21) and F2 (N=101) mice were assessed on postnatal days (P) 28 and 42 using photorefractometry. In a subset of mice (N=30-40), corneal radius of curvature, axial ocular dimensions, retinal and visual function were assessed. ResultsF2 mice were classified as NORE with either hyperopic (RE[≥]0 diopters (D) at P28 and P42), myopic (RE<0D at P28 and P42) or intermediate (RE<0D at P28 and RE[≥]0D at P42) refractions based on individual trajectories. All ocular parameters changed with age, with significantly slower growth in axial length and vitreous chamber depth in the intermediate versus myopic mice (p<0.05). Lens thickness was smaller in the myopic group at P28. Differences in refraction were not attributed to variances in retinal function or dopamine signaling. ConclusionsNORE mice represent a novel, genetically diverse wild-type mouse model that, unlike traditional models, does not require interventions such as FD or LIM to induce myopia. NORE mice provide a valuable tool for future investigations of genetic and environmental mechanisms and targeted therapeutic strategies for refractive errors.

genetics↗

bioRxiv2026

Circadian rhythms regulate refractive development across species

Myopia is a rapidly escalating global public health challenge, yet the biological mechanisms linking modern lifestyles to abnormal eye growth remain unclear. Circadian rhythms have been implicated in refractive development, but causal evidence is limited. Here, we integrate population-scale human data with an experimental animal model to determine whether circadian misalignment contributes to myopia. In >265,000 individuals from the Estonian and UK Biobanks, late chronotype was consistently associated with myopia. To assess causality, we experimentally disrupted the alignment between behavioural and environmental rhythms in mice by housing them in non-24-hour light-dark schedules. Exposure to a lengthened cycle (T26) induced a myopic shift that was, notably, reversible in early adulthood. Retinal transcriptomics revealed enrichment of mitochondrial and hypoxia-related plasticity pathways, with transcriptional changes distributed across multiple retinal cell classes. Together, these findings identify circadian misalignment as a conserved and modifiable driver of myopia, highlighting opportunities for novel preventive and therapeutic approaches.

neuroscience↗

bioRxiv2025

Effects of treadmill exercise on retinal vascular morphology, function, and circulating immune factors in a mouse model of retinal degeneration

PurposeExercise is neuroprotective in rodents undergoing retinal degeneration (RD). However, the effects of exercise on retinal vasculature remain unexplored. Here, we investigate whether treadmill exercise influences retinal vascular morphology, function, gene expression, and circulating factors in a light-induced retinal degeneration (LIRD) mouse model. Methods6-week-old female BALB/c mice were assigned to inactive+dim, active+dim, inactive+LIRD and active+LIRD groups (n=20 per group). Active mice were treadmill exercised (1hr/d 10m/min) for two weeks, then LIRD was induced (5000 lux/4hrs). Inactive mice were placed on a static treadmill. Retinal neurovascular coupling was measured with functional hyperemia (FH) and vascular morphology using OCT-A. Vascular gene expression was quantified from isolated retinal endothelial cells using ddPCR five days following LIRD. Serum was collected for circulating cytokine and chemokine analyses. Data were analyzed using 2-way ANOVA. ResultsRetinal vessel vasodilation was significantly increased in active+LIRD mice compared to inactive+LIRD mice. Superficial and intermediate/deep vascular plexi from inactive+LIRD mice had significantly decreased vessel density and total vessel length, with increased numbers of end points and lacunarity compared to active groups. Isolated retinal endothelial cell gene expression varied among groups. Most notably, Active+LIRD mice had a distinct immune response profile, with increased expression of IL-6, KC, and VEGF-A. ConclusionsTreadmill exercise maintained retinal vascular morphology and function, modestly altered endothelial gene expression, and is associated with a specific circulating immune response profile in a LIRD mouse model. These data indicate therapeutic effects of exercise on retinal vasculature in RD.

neuroscience↗

bioRxiv2025

Studies of all-trans retinoic acid transport in myopigenesis

PurposeMyopia incidence is increasing globally. All-trans retinoic acid (atRA) is important in myopigenic retinoscleral signaling, motivating research on its ocular transport. However, atRAs weak autofluorescence limits its direct visualization in tissues. Further, atRA is hydrophobic and must bind to protein carriers for transport. We assessed a fluorescent analog of atRA (LightOxTM14, CAS:198696-03-6, referred as floRA), as an experimentally accessible atRA surrogate by: (i) evaluating its binding to carrier proteins and (ii) visualizing its distribution in ocular tissues. MethodsO_ST_ABSBindingC_ST_ABSWe assessed atRA-carrier protein binding using fluorescence quenching assays with bovine serum albumin (BSA), high density lipoprotein (HDL), apolipoprotein A-I (Apo A-I) and retinol binding protein 4 (RBP4). Direct visualizationWild-type C57BL/6J mice were euthanized, eyes enucleated, and wedges containing sclera and choroid incubated for specific durations in 50 M floRA+BSA. The wedge centers were cryo-sectioned and counterstained for nuclei. Fluorescent micrographs were acquired and analyzed using ImageJ. ResultsAssociation constants (Ka) for atRA and floRA binding to carrier proteins were similar and ranged from 2-13 x 105 M-1, indicating non-specific binding. floRA could be visualized in sclera and choroid, yet showed significant spatial heterogeneity (enhanced fluorescence often colocalizing with nuclei). ConclusionsfloRA is a reasonable surrogate for atRA binding to BSA, HDL, Apo A-I and RBP4. Considering these proteins relative serum and extravascular abundances, and their similar binding affinity to atRA, we predict that serum albumin is an important atRA carrier. Use of floRA in whole tissue tracer studies shows promise but requires further refinement.

biochemistry↗

bioRxiv2024

Modulation of all-trans retinoic acid by light and dopamine in the murine eye

PurposeAmbient light exposure is linked to myopia development in children and affects myopia susceptibility in animal models. Currently, it is unclear which signals mediate the effects of light on myopia. All-trans retinoic acid (atRA) and dopamine (DA) oppositely influence experimental myopia and may be involved in the retino-scleral signaling cascade underlying myopic eye growth. However, how ocular atRA responds to different lighting and whether atRA and DA interact remains unknown. MethodsDark-adapted C57BL/6J mice (29-31 days old) were exposed to Dim (1 lux), Mid (59 lux), or Bright (12,000 lux) ambient lighting for 5-60 minutes. Some mice were also systemically administered the DA precursor, LDOPA, or atRA prior to light exposure. After exposure, the retina and the back-of-the-eye (BOE) were collected and analyzed for levels of atRA, DA, and the DA metabolite, DOPAC. ResultsDA turnover (DOPAC/DA ratio) in the retina increased in magnitude after only five minutes of exposure to higher ambient luminance but was minimal in the BOE. In contrast, atRA levels in the retina and BOE significantly decreased with higher ambient luminance and longer duration exposure. Intriguingly, LDOPA-treated mice had a transient reduction in retinal atRA compared to saline-treated mice, whereas atRA treatment had no effect on ocular DA. ConclusionsOcular atRA was affected by the duration of exposure to different ambient lighting and retinal atRA levels decreased with increased DA. Overall, these data suggest specific interactions between ambient lighting, atRA, and DA that could have implications for the retino-scleral signaling cascade underlying myopic eye growth.

systems biology↗

bioRxiv2021

Treadmill exercise promotes retinal astrocyte plasticity and protects against retinal degeneration

Exercise has been shown to be an effective neuroprotective intervention that preserves retinal function and structure in several animal models of retinal degeneration. However, retinal cell morphology and cell types governing exercise-induced retinal neuroprotection remain elusive. Previously, we found that the protective effects of exercise in animal models of retinal disease were accompanied by increased levels of circulating and retinal brain derived neurotrophic factor (BDNF) and required intact signal transduction with its high-affinity receptor, tropomyosin kinase B (TrkB). Studies of neurodegenerative diseases in the brain demonstrate that neurons and astrocytes express BDNF and TrkB. Additionally, astrocytes have been shown to alter their morphology in response to exercise. Here, we have investigated the role of retinal astrocytes as mediators of exercise-induced retinal neuroprotection in a light-induced retinal degeneration mouse model (LIRD). We found that treadmill exercise in both our dim (control maintenance light levels) and LIRD groups promote increased retinal astrocytic population, GFAP expression, branching and endpoints, dendritic complexity, and promotes BDNF-astrocyte interaction. In contrast, LIRD animals that were inactive had significant reductions in all measured parameters. Our findings indicate that exercise is sufficient to rescue retinal astrocyte morphology in a LIRD model maintaining branching and dendritic arborization similar to retinal astrocytes that are not undergoing degeneration. These studies provide essential information to current knowledge gaps in regards to exercise-induced neuroprotection and will additionally provide knowledge in exercise intervention optimization as a rehabilitative method. Significance statementThis study represents an essential step in determining the cell-types governing and morphological alterations elicited from exercise which may provide neural repair and protection. Similar to astrocytes in the brain, retinal astrocytes alter their morphology in response to exercise. Our studies demonstrate exercise promotes increased interactions between retinal astrocytes and neural growth factors in healthy retinas as well as in retinas undergoing degeneration, which may ultimately protect dying retinal neurons. These studies provide insight into the potential neuroprotective role astrocytes play in neurodegenerative diseases.

neuroscience↗

bioRxiv2020

A Biphasic Approach for Characterizing Tensile, Compressive, and Hydraulic Properties of the Sclera

Measuring the biomechanical properties of the mouse sclera is of great interest, since altered scleral properties are features of many common ocular pathologies, and the mouse is a powerful species for studying genetic factors in disease. Here, a poroelastic material model is used to analyze data from unconfined compression testing of both pig and mouse sclera, and the tensile modulus, compressive modulus, and permeability of the sclera are obtained at three levels of compressive strain. Values for all three properties measured simultaneously by unconfined compression of pig sclera were comparable to previously reported values measured by tests specific for each property, i.e., compression tests, biaxial tensile tests, and falling-head permeability assays. The repeatability of the approach was evaluated using test-retest experimental paradigm on pig sclera. Repeatability was low for measured compressive stiffness, indicating permanent changes to the samples occurring after the first test. However, reasonable repeatability for tensile stiffness and permeability was observed. The intrinsic material properties of the mouse sclera were measured for the first time. Tensile stiffness and permeability of the sclera in both species were seen to be dependent on the state of compressive strain. We conclude that unconfined compression testing of sclera, when analyzed with poroelastic theory, can be used as a powerful tool to phenotype mouse scleral changes in future genotype-phenotype association studies. Statement of SignificanceOcular biomechanics is strongly influenced by the sclera, the outermost white coat of the eye. Many ocular diseases are believed to be influenced by pathological changes to scleral microstructure and biomechanics, making intrinsic biomechanical properties an important outcome measure in many studies. However, the small mouse eye precludes the use of most traditional biomechanical characterization techniques. Here, we show that unconfined compression testing analyzed with poroelastic theory can produce measurements of biomechanical properties in the pig sclera comparable to those measured by other traditional techniques. Importantly, this technique can be successfully applied to the mouse sclera, enabling more widespread use of the species as a model for ocular disease.

bioengineering↗