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Pardue, M. T.

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

2 recordsLinked to original sources

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

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