283 results found
Safa BN, Read AT, Ethier CR, 2021, Assessment of the viscoelastic mechanical properties of the porcine optic nerve head using micromechanical testing and finite element modeling, ACTA BIOMATERIALIA, Vol: 134, Pages: 379-387, ISSN: 1742-7061
<jats:title>Abstract</jats:title><jats:p>Optic nerve head (ONH) biomechanics is centrally involved in the pathogenesis of glaucoma, a blinding ocular condition often characterized by elevation and fluctuation of the intraocular pressure and resulting loads on the ONH. Further, tissue viscoelasticity is expected to strongly influence the mechanical response of the ONH to mechanical loading, yet the viscoelastic mechanical properties of the ONH remain unknown. To determine these properties, we conducted micromechanical testing on porcine ONH tissue samples, coupled with finite element modeling based on a mixture model consisting of a biphasic material with a viscoelastic solid matrix. Our results provide a detailed description of the viscoelastic properties of the porcine ONH at each of its four anatomical quadrants (i.e., nasal, superior, temporal, and inferior). We showed that the ONH’s viscoelastic mechanical response can be explained by a dual mechanism of fluid flow and solid matrix viscoelasticity, as is common in other soft tissues. We obtained porcine ONH properties as follows: matrix Young’s modulus <jats:italic>E</jats:italic>=1.895 [1.056,2 .391] kPa (median [min., max.]), Poisson’s ratio <jats:italic>ν</jats:italic>=0.142 [0.060,0 .312], kinetic time-constant <jats:italic>τ</jats:italic>=214 [89,921] sec, and hydraulic permeability <jats:italic>k</jats:italic>=3.854 × 10<jats:sup>−1</jats:sup> [3.457 × 10<jats:sup>−2</jats:sup>,9.994 × 10<jats:sup>−1</jats:sup>] mm<jats:sup>4</jats:sup>/(N sec). These values can be used to design and fabricate physiologically appropriate <jats:italic>ex vivo</jats:italic> test environments (e.g., 3D cell culture) to further understand glaucoma pathophysiology.</jats:p>
Safa BN, Santare MH, Ethier CR, et al., 2021, Identifiability of tissue material parameters from uniaxial tests using multi-start optimization, ACTA BIOMATERIALIA, Vol: 123, Pages: 197-207, ISSN: 1742-7061
Zhu W, Hou F, Fang J, et al., 2021, The role of Piezo1 in conventional aqueous humor outflow dynamics, ISCIENCE, Vol: 24
Sater SH, Sass AM, Rohr JJ, et al., 2021, Automated MRI-based quantification of posterior ocular globe flattening and recovery after long-duration spaceflight, EYE, Vol: 35, Pages: 1869-1878, ISSN: 0950-222X
Brown DM, Pardue MT, Ethier CR, 2021, A biphasic approach for characterizing tensile, compressive and hydraulic properties of the sclera, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 18, ISSN: 1742-5689
Hannon BG, Feola AJ, Gerberich BG, et al., 2021, Using retinal function to define ischemic exclusion criteria for animal models of glaucoma, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, ISSN: 0014-4835
Lee C, Li G, Stamer WD, et al., 2021, In vivo estimation of murine iris stiffness using finite element modeling, EXPERIMENTAL EYE RESEARCH, Vol: 202, ISSN: 0014-4835
Rohr JJ, Sater S, Sass AM, et al., 2020, Quantitative magnetic resonance image assessment of the optic nerve and surrounding sheath after spaceflight, NPJ MICROGRAVITY, Vol: 6
Rohr JJ, Sater S, Sass AM, et al., 2020, Quantitative magnetic resonance image assessment of the optic nerve and surrounding sheath after spaceflight., NPJ Microgravity, Vol: 6, ISSN: 2373-8065
A subset of long-duration spaceflight astronauts have experienced ophthalmic abnormalities, collectively termed spaceflight-associated neuro-ocular syndrome (SANS). Little is understood about the pathophysiology of SANS; however, microgravity-induced alterations in intracranial pressure (ICP) due to headward fluid shifts is the primary hypothesized contributor. In particular, potential changes in optic nerve (ON) tortuosity and ON sheath (ONS) distension may indicate altered cerebrospinal fluid dynamics during weightlessness. The present longitudinal study aims to provide a quantitative analysis of ON and ONS cross-sectional areas, and ON deviation, an indication of tortuosity, before and after spaceflight. Ten astronauts undergoing ~6-month missions on the International Space Station (ISS) underwent high-resolution magnetic resonance imaging (MRI) preflight and at five recovery time points extending to 1 year after return from the ISS. The mean changes in ON deviation, ON cross-sectional area, and ONS cross-sectional area immediately post flight were -0.14 mm (95% CI: -0.36 to 0.08, Bonferroni-adjusted P = 1.00), 0.13 mm2 (95% CI -0.66 to 0.91, Bonferroni-adjusted P = 1.00), and -0.22 mm2 (95% CI: -1.78 to 1.34, Bonferroni-adjusted P = 1.00), respectively, and remained consistent during the recovery period. Terrestrially, ONS distension is associated with increased ICP; therefore, these results suggest that, on average, ICP was not pathologically elevated immediately after spaceflight. However, a subject diagnosed with optic disc edema (Frisen Grade 1, right eye) displayed increased ONS area post flight, although this increase is relatively small compared to clinical populations with increased ICP. Advanced quantitative MRI-based assessment of the ON and ONS could help our understanding of SANS and the role of ICP.
Brown DM, Pardue MT, Ethier CR, 2020, A Biphasic Approach for Characterizing Tensile, Compressive, and Hydraulic Properties of the Sclera
<jats:title>Abstract</jats:title><jats:p>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.</jats:p><jats:sec><jats:title>Statement of Significance</jats:title><jats:p>Ocular 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
Schwaner SA, Hannon BG, Feola AJ, et al., 2020, Biomechanical properties of the rat sclera obtained with inverse finite element modeling, BIOMECHANICS AND MODELING IN MECHANOBIOLOGY, Vol: 19, Pages: 2195-2212, ISSN: 1617-7959
Schwaner SA, Feola AJ, Ethier CR, 2020, Factors affecting optic nerve head biomechanics in a rat model of glaucoma, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 17, ISSN: 1742-5689
Hannon BG, Schwaner SA, Boazak EM, et al., 2019, Sustained scleral stiffening in rats after a single genipin treatment, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 16, ISSN: 1742-5689
Snider EJ, Kubelick KP, Tweed K, et al., 2018, Improving Stem Cell Delivery to the Trabecular Meshwork Using Magnetic Nanoparticles, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322
Feola AJ, Nelson ES, Myers J, et al., 2018, The Impact of Choroidal Swelling on Optic Nerve Head Deformation, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 59, Pages: 4172-4181, ISSN: 0146-0404
Keller KE, Bhattacharya SK, Borras T, et al., 2018, Consensus recommendations for trabecular meshwork cell isolation, characterization and culture, EXPERIMENTAL EYE RESEARCH, Vol: 171, Pages: 164-173, ISSN: 0014-4835
Wang K, Li G, Read AT, et al., 2018, The relationship between outflow resistance and trabecular meshwork stiffness in mice, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322
Snider EJ, Vannatta RT, Schildmeyer L, et al., 2018, Characterizing differences between MSCs and TM cells: Toward autologous stem cell therapies for the glaucomatous trabecular meshwork, JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol: 12, Pages: 695-704, ISSN: 1932-6254
Mulvihill JJE, Raykin J, Snider EJ, et al., 2018, Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels, ANNALS OF BIOMEDICAL ENGINEERING, Vol: 46, Pages: 365-374, ISSN: 0090-6964
Campbell IC, Sherwood JM, Overby DR, et al., 2017, Quantification of Scleral Biomechanics and Collagen Fiber Alignment., Glaucoma. Methods in Molecular Biology., Editors: Jakobs, Publisher: Humana Press, Pages: 135-159
The stiffness of the sclera is important in several ocular disorders, and there is hence a need to quantify the biomechanical properties of this tissue. Here, we present two methods for measuring the stiffness of scleral ocular tissues: ocular compliance testing and digital image correlation strain mapping. In tandem with these approaches, we provide two methods to spatially quantify the anisotropic alignment of collagen fibers making up the sclera, using second harmonic generation microscopy and small-angle light scattering. Together, these approaches allow specimen-specific measurement of tissue stiffness and collagen alignment, which are key factors in determining how the eye responds to mechanical loads.
Perea D, Guiu J, Hudry B, et al., 2017, Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia., EMBO Journal, Vol: 36, Pages: 3029-3045, ISSN: 0261-4189
Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homoeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease.
Wang K, Johnstone MA, Xin C, et al., 2017, Estimating Human Trabecular Meshwork Stiffness by Numerical Modeling and Advanced OCT Imaging, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 58, Pages: 4809-4817, ISSN: 0146-0404
Nelson ES, Mulugeta L, Feola A, et al., 2017, The impact of ocular hemodynamics and intracranial pressure on intraocular pressure during acute gravitational changes, JOURNAL OF APPLIED PHYSIOLOGY, Vol: 123, Pages: 352-363, ISSN: 8750-7587
Chang JYH, Chow LW, Dismuke WM, et al., 2017, Peptide-functionalized fluorescent particles for in situ detection of nitric oxide via peroxynitrite-mediated nitration, Advanced Healthcare Materials, Vol: 6, ISSN: 2192-2640
Nitric oxide (NO) is a free radical signaling molecule that plays a crucial role in modulating physiological homeostasis across multiple biological systems. NO dysregulation is linked to the pathogenesis of multiple diseases; therefore, its quantification is important for understanding pathophysiological processes. The detection of NO is challenging, typically limited by its reactive nature and short half-life. Additionally, the presence of interfering analytes and accessibility to biological fluids in the native tissues make the measurement technically challenging and often unreliable. Here, a bio-inspired peptide-based NO sensor is developed, which detects NO-derived oxidants, predominately peroxynitrite-mediated nitration of tyrosine residues. It is demonstrated that these peptide-based NO sensors can detect peroxynitrite-mediated nitration in response to physiological shear stress by endothelial cells in vitro. Using the peptide-conjugated fluorescent particle immunoassay, peroxynitrite-mediated nitration activity with a detection limit of ≈100 × 10−9m is detected. This study envisions that the NO detection platform can be applied to a multitude of applications including monitoring of NO activity in healthy and diseased tissues, localized detection of NO production of specific cells, and cell-based/therapeutic screening of peroxynitrite levels to monitor pronitroxidative stress in biological samples.
Campbell IC, Hannon BG, Read AT, et al., 2017, Quantification of the efficacy of collagen cross-linking agents to induce stiffening of rat sclera (vol 14, 20170014, 2017), Journal of the Royal Society Interface, Vol: 14, ISSN: 1742-5662
The concept of scleral stiffening therapies has emerged as a novel theoretical approach for treating the ocular disorders glaucoma and myopia. Deformation of specific regions of the posterior eye is innately involved in the pathophysiology of these diseases, and thus targeted scleral stiffening could resist these changes and slow or prevent progression of these diseases. Here, we present the first systematic screen and direct comparison of the stiffening effect of small molecule collagen cross-linking agents in the posterior globe, namely using glyceraldehyde, genipin and methylglyoxal (also called pyruvaldehyde). To establish a dose–response relationship, we used inflation testing to simulate the effects of increasing intraocular pressure in freshly harvested rat eyes stiffened with multiple concentrations of each agent. We used digital image correlation to compute the mechanical strain in the tissue as a metric of stiffness, using a novel treatment paradigm for screening relative stiffening by incubating half of each eye in cross-linker and using the opposite half as an internal control. We identified the doses necessary to increase stiffness by approximately 100%, namely 30 mM for glyceraldehyde, 1 mM for genipin and 7 mM for methylglyoxal, and we also identified the range of stiffening it was possible to achieve with such agents. Such findings will inform development of in vivo studies of scleral stiffening to treat glaucoma and myopia.
Stowell C, Burgoyne CF, Tamm ER, et al., 2017, Biomechanical aspects of axonal damage in glaucoma: A brief review, EXPERIMENTAL EYE RESEARCH, Vol: 157, Pages: 13-19, ISSN: 0014-4835
Tamm ER, Ethier CR, 2017, Biological aspects of axonal damage in glaucoma: A brief review, EXPERIMENTAL EYE RESEARCH, Vol: 157, Pages: 5-12, ISSN: 0014-4835
Feola AJ, Coudrillier B, Mulvihill J, et al., 2017, Deformation of the Lamina Cribrosa and Optic Nerve Due to Changes in Cerebrospinal Fluid Pressure, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 58, Pages: 2070-2078, ISSN: 0146-0404
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.