Imperial College London
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ProfessorDarrylOverby

Faculty of Engineering, Department of Bioengineering

Professor of Mechanobiology
 
 
 
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Contact

 

+44 (0)20 7594 6376d.overby

 
 
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Location

 

3.07Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

166 results found

Ashpole NE, Overby DR, Ethier CR, Stamer WDet al., 2014, Shear Stress-Triggered Nitric Oxide Release From Schlemm's Canal Cells, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 55, Pages: 8067-8076, ISSN: 0146-0404

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

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

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

Chang JYH, Ethier CR, Stamer WD, Overby DRet al., 2014, Differential effects of nitric oxide synthase inhibitors on conventional outflow facility in mice, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Braakman ST, Stamer WD, Overby DR, 2014, A fluorescent permeability assay for Schlemm's canal endothelial cells in response to stretch, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Wen JC, Overby DR, Madekurozwa M, Chu B, Mettu PS, Schuman SG, Challa P, Cousins SW, Allingham RRet al., 2014, The effect of anti-VEGF injections on tonographic aqueous outflow facility and a novel method to calculate facility using the post-injection IOP decay curve, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Liu KC, Li G, Overby DR, Stamer WDet al., 2014, Role of VEGF in Conventional Outflow Homeostasis, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Reina-Torres E, Sherwood JM, Stamer WD, Overby DRet al., 2014, Role of Vascular Endothelial Growth Factor (VEGF) in the regulation of conventional outflow facility in mice, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Overby DR, Vahabikashi A, Vargas-Pinto R, Braakman ST, Pedrigi R, Gupta R, Perkumas KM, Stamer WD, Ethier CR, Johnson Met al., 2014, The Effect of Cell Stiffness on I- and B-Pore Formation in Schlemm's Canal Endothelial Cells, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

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 OF OCULAR PHARMACOLOGY AND THERAPEUTICS, Vol: 30, Pages: 213-223, ISSN: 1080-7683

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

Journal article

Ethier C, Braakman S, Read A, Chan D, Overby Det al., 2013, Schlemm's Canal (SC) Inner Wall Pores Correlate with Segmental Outflow in Human Eyes, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Ashpole N, Overby D, Ethier C, Stamer WDet al., 2013, Shear Stress Stimulation of NO release from Schlemm's Canal Cells, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Luetjen-Drecoll E, Tektas O, Overby D, 2013, Three-dimensional structure of the mouse ciliary muscle, its innervation and connections to the outflow tissues and choroid, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Calleja AB, Stamer WD, Ethier C, Overby Det al., 2013, Metabolic Dependence of Conventional Outflow Facility in Mice, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Braakman S, Perkumas K, Overby D, Woodward D, Stamer WDet al., 2013, Sphingosine-1-Phosphate signaling in cultured human trabecular meshwork cells, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Johnson M, Pedrigi R, Vargas-Pinto R, Gupta R, Braakman S, Ethier C, Perkumas K, Stamer WD, Overby Det al., 2013, Elevated stiffness of cultured glaucomatous Schlemm's canal (SC) cells correlates with impaired pore formation, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Overby D, Bertrand J, Tektas O, Calleja AB, Stamer WD, Ethier C, Woodward D, Luetjen-Drecoll Eet al., 2013, Functional and Morphological Alterations Associated with Steroid-Induced Ocular Hypertension in Mice, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Chang J, Marando C, Ethier C, Stamer WD, Overby Det al., 2013, Effects of Nitric Oxide Donor on Outflow Facility in Mice, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

Amin HD, Brady MA, St-Pierre J-P, Stevens MM, Overby DR, Ethier CRet al., 2013, STIMULATION OF CHONDROGENIC DIFFERENTIATION OF ADULT HUMAN PRECURSOR CELLS USING STATIC MAGNETIC FIELD AS A PHYSICAL CUE, World Congress of the Osteoarthritis-Research-Society-International (OARSI), Publisher: ELSEVIER SCI LTD, Pages: S118-S118, ISSN: 1063-4584

Conference paper

Vargas-Pinto R, Pedrigi RM, Braakman S, Gupta R, Vahabikashi A, Perkumas K, Ethier CR, Stamer WD, Overby DR, Johnson Met al., 2013, Cultured glaucomatous Schlemm's canal cells show increased subcortical stiffness and decreased pore density., MOLECULAR BIOLOGY OF THE CELL, Vol: 24, ISSN: 1059-1524

Journal article

Francis AW, Kagemann L, Wollstein G, Ishikawa H, Folz S, Overby DR, Sigal IA, Wang B, Schuman JSet al., 2012, Morphometric Analysis of Aqueous Humor Outflow Structures with Spectral-Domain Optical Coherence Tomography, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 53, Pages: 5198-5207, ISSN: 0146-0404

Journal article

Boussommier-Calleja A, Bertrand J, Woodward DF, Ethier CR, Stamer WD, Overby DRet al., 2012, Pharmacologic Manipulation of Conventional Outflow Facility in Ex Vivo Mouse Eyes, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 53, Pages: 5838-5845, ISSN: 0146-0404

Journal article

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