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  • Journal article
    Stamer WD, Braakman ST, Zhou EH, Ethier CR, Fredberg JJ, Overby DR, Johnson Met al., 2015,

    Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction

    , PROGRESS IN RETINAL AND EYE RESEARCH, Vol: 44, Pages: 86-98, ISSN: 1350-9462
  • Journal article
    Overby DR, Zhou EH, Vargas-Pinto R, Pedrigi RM, Fuchshofer R, Braakman ST, Gupta R, Perkumas KM, Sherwood JM, Vahabikashi A, Quynh D, Kim JH, Ethier CR, Stamer WD, Fredberg JJ, Johnson Met al., 2014,

    Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma

    , Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 13876-13881, ISSN: 0027-8424

    Increased flow resistance is responsible for the elevated intraocular pressure characteristic of glaucoma, but the cause of this resistance increase is not known. We tested the hypothesis that altered biomechanical behavior of Schlemm’s canal (SC) cells contributes to this dysfunction. We used atomic force microscopy, optical magnetic twisting cytometry, and a unique cell perfusion apparatus to examine cultured endothelial cells isolated from the inner wall of SC of healthy and glaucomatous human eyes. Here we establish the existence of a reduced tendency for pore formation in the glaucomatous SC cell—likely accounting for increased outflow resistance—that positively correlates with elevated subcortical cell stiffness, along with an enhanced sensitivity to the mechanical microenvironment including altered expression of several key genes, particularly connective tissue growth factor. Rather than being seen as a simple mechanical barrier to filtration, the endothelium of SC is seen instead as a dynamic material whose response to mechanical strain leads to pore formation and thereby modulates the resistance to aqueous humor outflow. In the glaucomatous eye, this process becomes impaired. Together, these observations support the idea of SC cell stiffness—and its biomechanical effects on pore formation—as a therapeutic target in glaucoma.

  • Journal article
    Braakman ST, Pedrigi RM, Read AT, Smith JAE, Stamer WD, Ethier CR, Overby DRet al., 2014,

    Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells

    , Experimental Eye Research, Vol: 127, Pages: 224-235, ISSN: 1096-0007

    The bulk of aqueous humor passing through the conventional outflow pathway must cross the inner wall endothelium of Schlemm's canal (SC), likely through micron-sized transendothelial pores. SC pore density is reduced in glaucoma, possibly contributing to obstructed aqueous humor outflow and elevated intraocular pressure (IOP). Little is known about the mechanisms of pore formation; however, pores are often observed near dome-like cellular outpouchings known as giant vacuoles (GVs) where significant biomechanical strain acts on SC cells. We hypothesize that biomechanical strain triggers pore formation in SC cells. To test this hypothesis, primary human SC cells were isolated from three non-glaucomatous donors (aged 34, 44 and 68), and seeded on collagen-coated elastic membranes held within a membrane stretching device. Membranes were then exposed to 0%, 10% or 20% equibiaxial strain, and the cells were aldehyde-fixed 5 min after the onset of strain. Each membrane contained 3-4 separate monolayers of SC cells as replicates (N = 34 total monolayers), and pores were assessed by scanning electron microscopy in 12 randomly selected regions (∼65,000 μm2 per monolayer). Pores were identified and counted by four independent masked observers. Pore density increased with strain in all three cell lines (p < 0.010), increasing from 87 ± 36 pores/mm2 at 0% strain to 342 ± 71 at 10% strain; two of the three cell lines showed no additional increase in pore density beyond 10% strain. Transcellular “I-pores” and paracellular “B-pores” both increased with strain (p < 0.038), however B-pores represented the majority (76%) of pores. Pore diameter, in contrast, appeared unaffected by strain (p = 0.25), having a mean diameter of 0.40 μm for I-pores (N = 79 pores) and 0.67 μm for B-pores (N = 350 pores). Pore formation appears to be a mechanosensitive process that is triggered by biomechanical strain, suggesting that SC cells have th

  • Journal article
    Overby DR, Bertrand J, Tektas O-Y, Boussommier-Calleja A, Schicht M, Ethier CR, Woodward DF, Stamer WD, Luetjen-Drecoll Eet al., 2014,

    Ultrastructural Changes Associated With Dexamethasone-Induced Ocular Hypertension in Mice

    , INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 55, Pages: 4922-4933, ISSN: 0146-0404
  • Journal article
    Ma S, Sherwood JM, Huck WTS, Balabani Set al., 2014,

    On the flow topology inside droplets moving in rectangular microchannels

    , Lab on a Chip, Vol: 14, Pages: 3611-3620, ISSN: 1473-0197

    The flow topology in moving microdroplets has a significant impact on the behaviour of encapsulated objects and hence on applications of the technology. This study reports on a systematic investigation of the flow field inside droplets moving in a rectangular microchannel, by means of micro-particle image velocimetry (μPIV). Various water/oil (w/o) fluid mixtures were studied in order to elucidate the effects of a number of parameters such as capillary number (Ca), droplet geometry, viscosity ratio and interfacial tension. A distinct change in flow topology was observed at intermediate Ca ranging from 10−3 to 10−1, in surfactant-laden droplets, which was attributed primarily to the viscosity ratio of the two phases rather than the Marangoni effect expected in such systems. W/o droplet systems of lower inner-to-outer viscosity ratios tend to exhibit the well-known flow pattern characterised by a parabola-like profile in the droplet bulk-volume, surrounded by two counter rotating recirculation zones on either side of the droplet axis. As the viscosity ratio between the two phases is increased, the flow pattern becomes more uniform, exhibiting low velocities in the droplet bulk-volume and higher-reversed velocities along the w/o interface. The Ca and droplet geometry had no effect on the observed flow topology change. The study highlights the complex, three-dimensional (3D) nature of the flow inside droplets in rectangular microchannels and demonstrates the ability to control the droplet flow environment by adjusting the viscosity ratio between the two phases.

  • Journal article
    Sherwood JM, Holmes D, Kaliviotis E, Balabani Set al., 2014,

    Spatial Distributions of Red Blood Cells Significantly Alter Local Haemodynamics

    , PLOS ONE, Vol: 9, ISSN: 1932-6203
  • Journal article
    Overby DR, Bertrand J, Schicht M, Paulsen F, Stamer WD, Luetjen-Drecoll Eet al., 2014,

    The Structure of the Trabecular Meshwork, Its Connections to the Ciliary Muscle, and the Effect of Pilocarpine on Outflow Facility in Mice

    , INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 55, Pages: 3727-3736, ISSN: 0146-0404
  • Journal article
    Li G, Farsiu S, Chiu SJ, Gonzalez P, Luetjen-Drecoll E, Overby DR, Stamer WDet al., 2014,

    Pilocarpine-Induced Dilation of Schlemm's Canal and Prevention of Lumen Collapse at Elevated Intraocular Pressures in Living Mice Visualized by OCT

    , INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 55, Pages: 3737-3746, ISSN: 0146-0404
  • Journal article
    Sherwood JM, Kaliviotis E, Dusting J, Balabani Set al., 2014,

    Hematocrit, viscosity and velocity distributions of aggregating and non-aggregating blood in a bifurcating microchannel

    , BIOMECHANICS AND MODELING IN MECHANOBIOLOGY, Vol: 13, Pages: 259-273, ISSN: 1617-7959
  • Journal article
    Chang JYH, Folz SJ, Laryea SN, Overby DRet al., 2014,

    Multi-Scale Analysis of Segmental Outflow Patterns in Human Trabecular Meshwork with Changing Intraocular Pressure

  • Journal article
    Dismuke WM, Liang J, Overby DR, Stamer WDet al., 2014,

    Concentration-related. effects of nitric oxide and endothelin-1 on human trabecular meshwork cell contractility

    , EXPERIMENTAL EYE RESEARCH, Vol: 120, Pages: 28-35, ISSN: 0014-4835
  • Journal article
    Amin HD, Brady MA, St-Pierre J-P, Stevens MM, Overby DR, Ethier CRet al., 2014,

    Stimulation of chondrogenic differentiation of adult human bone marrow-derived stromal cells by a moderate-strength static magnetic field

    , Tissue Engineering: Parts A, B, and C, Vol: 20, Pages: 1612-1620, ISSN: 1937-3368

    Tissue-engineering strategies for the treatment of osteoarthritis would benefit from the ability to induce chondrogenesis in precursor cells. One such cell source is bone marrow-derived stromal cells (BMSCs). Here, we examined the effects of moderate-strength static magnetic fields (SMFs) on chondrogenic differentiation in human BMSCs in vitro. Cells were cultured in pellet form and exposed to several strengths of SMFs for various durations. mRNA transcript levels of the early chondrogenic transcription factor SOX9 and the late marker genes ACAN and COL2A1 were determined by reverse transcription–polymerase chain reaction, and production of the cartilage-specific macromolecules sGAG, collage type 2 (Col2), and proteoglycans was determined both biochemically and histologically. The role of the transforming growth factor (TGF)-β signaling pathway was also examined. Results showed that a 0.4 T magnetic field applied for 14 days elicited a strong chondrogenic differentiation response in cultured BMSCs, so long as TGF-β3 was also present, that is, a synergistic response of a SMF and TGF-β3 on BMSC chondrogenic differentiation was observed. Further, SMF alone caused TGF-β secretion in culture, and the effects of SMF could be abrogated by the TGF-β receptor blocker SB-431542. These data show that moderate-strength magnetic fields can induce chondrogenesis in BMSCs through a TGF-β-dependent pathway. This finding has potentially important applications in cartilage tissue-engineering strategies.

  • Journal article
    Brady MA, Vaze R, Amin HD, Overby DR, Ethier CRet al., 2014,

    The Design and Development of a High-Throughput Magneto-Mechanostimulation Device for Cartilage Tissue Engineering

    , TISSUE ENGINEERING PART C-METHODS, Vol: 20, Pages: 149-159, ISSN: 1937-3384
  • Journal article
    Boussommier-Calleja A, Overby DR, 2013,

    The Influence of Genetic Background on Conventional Outflow Facility in Mice

    , INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 54, Pages: 8251-8258, ISSN: 0146-0404
  • Journal article
    Overby D, 2013,

    Basic science behind trabecular meshwork surgeries

    , ACTA OPHTHALMOLOGICA, Vol: 91, ISSN: 1755-375X

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