Publications
425 results found
Tam LC, Reina-Torres E, Sherwood JM, et al., 2017, Enhancement of outflow facility in the murine eye by targeting selected tight-junctions of Schlemm's canal endothelia, Scientific Reports, Vol: 7, ISSN: 2045-2322
The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm’s canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junctions (TJs), down-regulation of which may widen paracellular spaces between cells, allowing greater fluid outflow. We observed significant increase in paracellular permeability following siRNA-mediated suppression of TJ transcripts, claudin-11, zonula-occludens-1 (ZO-1) and tricellulin in human SC endothelial monolayers. In mice claudin-11 was not detected, but intracameral injection of siRNAs targeting ZO-1 and tricellulin increased outflow facility significantly. Structural qualitative and quantitative analysis of SC inner wall by transmission electron microscopy revealed significantly more open clefts between endothelial cells treated with targeting, as opposed to non-targeting siRNA. These data substantiate the concept that the continuity of SC endothelium is an important determinant of outflow resistance, and suggest that SC endothelial TJs represent a specific target for enhancement of aqueous movement through the conventional outflow system.
Chiang B, Wang K, Ethier CR, et al., 2017, Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 58, Pages: 545-554, ISSN: 0146-0404
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- Citations: 28
Kubelick K, Snider E, Yoon H, et al., 2017, Ultrasound and photoacoustic imaging to monitor ocular stem cell delivery and tissue regeneration (Conference Presentation), Conference on Photons Plus Ultrasound - Imaging and Sensing, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X
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- Citations: 1
Snider EJ, Kubelick K, Yoon H, et al., 2016, Nanoparticle-assisted Stem Cell Delivery in the Eye, TERMIS - Americas Conference and Exhibition, Publisher: MARY ANN LIEBERT, INC, Pages: S153-S153, ISSN: 1937-3341
Vicente KJ, Ethier CR, 2016, Why fluid dynamics matters for display design in process control: Commentary on Bennett and Malek, HUMAN FACTORS, Vol: 42, Pages: 451-454, ISSN: 0018-7208
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- Citations: 1
Wang K, Johnstone MA, Xin C, et al., 2016, Estimating human trabecular meshwork stiffness by numerical modeling and advanced OCT imaging, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Snider E, Vannatta RT, Stainer WD, et al., 2016, Co-Culture Stimulated Differentiation of Mesenchymal Stem Cells to Trabecular Meshwork Cells, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Mulvihill JJE, Schildmeyer LA, Raykin J, et al., 2016, Development of a platform for studying astrocyte mechanobiology in 3D culture, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Ashpole NE, Mukherjee D, Li G, et al., 2016, IOP-induced Changes in Schlemm's Canal Dimensions and the Relation to Shear Stress, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Feola A, Allen RS, Campbell IC, et al., 2016, Effects of Age and Ovariectomy on Visual Function in Experimental Glaucoma, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Campbell IC, Allen RS, Feola A, et al., 2016, Voluntary Exercise for Neuroprotection in Glaucoma, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Schwaner SA, Pazos M, Yang H, et al., 2016, Finite Element (FE) Modeling of Optic Nerve Head (ONH) Biomechanics in a Rat Model of Glaucoma, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Coudrillier B, Campbell IC, Read AT, et al., 2016, Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 57, Pages: 2666-2677, ISSN: 0146-0404
Feola AJ, Myers JG, Raykin J, et al., 2016, Finite Element Modeling of Factors Influencing Optic Nerve Head Deformation Due to Intracranial Pressure, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 57, Pages: 1901-1911, ISSN: 0146-0404
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- Citations: 61
Stockslager MA, Samuels BC, Allingham RR, et al., 2016, System for Rapid, Precise Modulation of Intraocular Pressure, toward Minimally-Invasive <i>In Vivo</i> Measurement of Intracranial Pressure, PLOS ONE, Vol: 11, ISSN: 1932-6203
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- Citations: 19
Brady MA, Talvard L, Vella A, et al., 2015, Bio-inspired design of a magnetically active trilayered scaffold for cartilage tissue engineering, Journal of Tissue Engineering and Regenerative Medicine, Vol: 11, Pages: 1298-1302, ISSN: 1932-6254
An important topic in cartilage tissue engineering is the development of biomimetic scaffolds which mimic the depth/dependent material properties of the native tissue. We describe an advanced trilayered nanocomposite hydrogel (ferrogel) with a gradient in compressive modulus from the top to the bottom layers (p<0.05) of the construct. Further, the scaffold was able to respond to remote external stimulation,exhibiting an elastic, depth/dependent strain gradient. When bovine chondrocytes were seeded into the ferrogels and cultured for up to 14 days, there was good cell viability and a biochemical gradient was measured with sulfated glycosaminoglycan increasing with depth from the surface. This novel construct provides tremendous scope for tailoring location/specific cartilage replacement tissue; by varying the density of magnetic nanoparticles, concentration of base hydrogel and number of cells, physiologically relevant depth/dependent gradients may be attained.
Braakman ST, Moore JE, Ethier CR, et al., 2015, Transport across Schlemm's canal endothelium and the blood-aqueous barrier, Experimental Eye Research, Vol: 146, Pages: 17-21, ISSN: 0014-4835
The majority of trabecular outflow likely crosses Schlemm's canal (SC) endothelium through micron-sized pores, and SC endothelium provides the only continuous cell layer between the anterior chamber and episcleral venous blood. SC endothelium must therefore be sufficiently porous to facilitate outflow, while also being sufficiently restrictive to preserve the blood-aqueous barrier and prevent blood and serum proteins from entering the eye. To understand how SC endothelium satisfies these apparently incompatible functions, we examined how the diameter and density of SC pores affects retrograde diffusion of serum proteins across SC endothelium, i.e. from SC lumen into the juxtacanalicular tissue (JCT). Opposing retrograde diffusion is anterograde bulk flow velocity of aqueous humor passing through pores, estimated to be approximately 5 mm/s. As a result of this relatively large through-pore velocity, a mass transport model predicts that upstream (JCT) concentrations of larger solutes such as albumin are less than 1% of the concentration in SC lumen. However, smaller solutes such as glucose are predicted to have nearly the same concentration in the JCT and SC. In the hypothetical case that, rather than micron-sized pores, SC formed 65 nm fenestrae, as commonly observed in other filtration-active endothelia, the predicted concentration of albumin in the JCT would increase to approximately 50% of that in SC. These results suggest that the size and density of SC pores may have developed to allow SC endothelium to maintain the blood-aqueous barrier while simultaneously facilitating aqueous humor outflow.
Boussommier-Calleja A, Li G, Wilson A, et al., 2015, Physical factors affecting outflow facility measurements in mice, Investigative Ophthalmology & Visual Science, Vol: 56, Pages: 8331-8339, ISSN: 1552-5783
Purpose: Mice are commonly used to study conventional outflow physiology. This study examined how physical factors (hydration, temperature, and anterior chamber [AC] deepening) influence ocular perfusion measurements in mice.Methods: Outflow facility (C) and pressure-independent outflow (Fu) were assessed by multilevel constant pressure perfusion of enucleated eyes from C57BL/6 mice. To examine the effect of hydration, seven eyes were perfused at room temperature, either immersed to the limbus in saline and covered with wet tissue paper or exposed to room air. Temperature effects were examined in 12 eyes immersed in saline at 20°C or 35°C. Anterior chamber deepening was examined in 10 eyes with the cannula tip placed in the anterior versus posterior chamber (PC). Posterior bowing of the iris (AC deepening) was visualized by three-dimensional histology in perfusion-fixed C57BL/6 eyes and by spectral-domain optical coherence tomography in living CD1 mice.Results: Exposure to room air did not significantly affect C, but led to a nonzero Fu that was significantly reduced upon immersion in saline. Increasing temperature from 20°C to 35°C increased C by 2.5-fold, more than could be explained by viscosity changes alone (1.4-fold). Perfusion via the AC, but not the PC, led to posterior iris bowing and increased outflow.Conclusions: Insufficient hydration contributes to the appearance of pressure-independent outflow in enucleated mouse eyes. Despite the large lens, AC deepening may artifactually increase outflow in mice. Temperature-dependent metabolic processes appear to influence conventional outflow regulation. Physical factors should be carefully controlled in any outflow studies involving mice.
Ethier CR, Morrison JC, Clark AF, 2015, Introduction to special issue on glaucomatous optic neuropathy: In vivo models and techniques, EXPERIMENTAL EYE RESEARCH, Vol: 141, Pages: 1-2, ISSN: 0014-4835
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- Citations: 2
Nguyen TD, Ethier CR, 2015, Biomechanical assessment in models of glaucomatous optic neuropathy, EXPERIMENTAL EYE RESEARCH, Vol: 141, Pages: 125-138, ISSN: 0014-4835
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- Citations: 24
Amin HD, Ethier CR, 2015, Differential effects of tyrosine-rich amelogenin peptide on chondrogenic and osteogenic differentiation of adult chondrocytes, Cell and Tissue Research, Vol: 364, Pages: 219-224, ISSN: 1432-0878
Current approaches to treat osteoarthritis (OA) are insufficient. Autologous chondrocyte implantation (ACI) has been used for the past decade to treat patients with OA or focal cartilage defects. However, a number of complications have been reported post-ACI, including athrofibrosis and symptomatic hypertrophy. Thus, a long term ACI strategy should ideally incorporate methods to ‘prime’ autologous chondrocytes to form cartilage-specific matrix and suppress hypertrophic mineralization. The objective of this study was to examine the effects of tyrosine rich amelogenin peptide (TRAP; an isoform of the develop mental protein amelogenin) on human articular cartilage cell (HAC) chondrogenic differentiation and hypertrophic mineralization in vitro. Effects of chemically synthesized TRAP on HAC chondrogenic differentiation were determined by assessing: (i) sGAG production; (ii) Alcian blue staining for proteoglycans; (iii) Collagen type II immunostaining; and (iv) Expression of the chondrogenic genes SOX9, ACAN and COL2A1. Hypertrophic mineralization was assayed by: (i) ALP expression; (ii) Alizarin red staining for Ca+2 -rich bone nodules; (iii) OC immunostaining; and (iv) Expression of the Osteogenic/Hypertrophic genes Ihh and BSP. Chemically synthesized TRAP was found to suppress terminal osteogenic differentiation of HACs cultured in hype rtrophic mineralization-like conditions, an effect mediated via down regulation of the Ihh gene. Moreover, TRAP was found to augment chondrogenic differentiation of HACs via induction of SOX9 gene expression when cells were cultured in pro-chondrogenic media. The results obtained from this proof of concept study motivate further studies on the use of TRAP as part of a preconditioning regimen in autologous chondrocyte implantation procedures for OA patients and patients suffering from focal cartilage defects.
Snider EJ, Pride C, Stamer WD, et al., 2015, Assessing Differences between Mesenchymal Stem Cells and Trabecular Meshwork Cells, 4th TERMIS World Congress, Publisher: MARY ANN LIEBERT, INC, Pages: S236-S236, ISSN: 1937-3341
Chang JYH, Stamer WD, Bertrand J, et al., 2015, Role of nitric oxide in murine conventional outflow physiology, American Journal of Physiology - Cell Physiology, Vol: 309, Pages: C205-C214, ISSN: 0363-6143
Elevated intraocular pressure (IOP) is the main risk factor for glaucoma. Exogenous nitric oxide (NO) decreases IOP by increasing outflow facility, but whether endogenous NO production contributes to the physiological regulation of outflow facility is unclear. Outflow facility was measured by pressure-controlled perfusion in ex vivo eyes from C57BL/6 wild-type (WT) or transgenic mice expressing human endothelial NO synthase (eNOS) fused to green fluorescent protein (GFP) superimposed on the endogenously expressed murine eNOS (eNOS-GFPtg). In WT mice, exogenous NO delivered by 100 μM S-nitroso-N-acetylpenicillamine (SNAP) increased outflow facility by 62 ± 28% (SD) relative to control eyes perfused with the inactive SNAP analog N-acetyl-d-penicillamine (NAP; n = 5, P = 0.016). In contrast, in eyes from eNOS-GFPtg mice, SNAP had no effect on outflow facility relative to NAP (−9 ± 4%, P = 0.40). In WT mice, the nonselective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10 μM) decreased outflow facility by 36 ± 13% (n = 5 each, P = 0.012), but 100 μM l-NAME had no detectable effect on outflow facility (−16 ± 5%, P = 0.22). An eNOS-selective inhibitor (cavtratin, 50 μM) decreased outflow facility by 19 ± 12% in WT (P = 0.011) and 39 ± 25% in eNOS-GFPtg (P = 0.014) mice. In the conventional outflow pathway of eNOS-GFPtg mice, eNOS-GFP expression was localized to endothelial cells lining Schlemm's canal and the downstream vessels, with no apparent expression in the trabecular meshwork. These results suggest that endogenous NO production by eNOS within endothelial cells of Schlemm's canal or downstream vessels contributes to the physiological regulation of aqueous humor outflow facility in mice, representing a viable strategy to more successfully lower IOP in glaucoma.
Vargas-Pinto R, Lai J, Gong H, et al., 2015, Finite element analysis of the pressure-induced deformation of Schlemm's canal endothelial cells, BIOMECHANICS AND MODELING IN MECHANOBIOLOGY, Vol: 14, Pages: 851-863, ISSN: 1617-7959
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- Citations: 5
Snider E, Pride C, Patil A, et al., 2015, Characterization of Mesenchymal Stem Cells vs. Trabecular Meshwork Cells, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Gonzalez P, Luna CC, Campbell I, et al., 2015, Protective Effects of Adenoviral Mediated Subconjunctival Delivery of BMP2 in an Experimental Glaucoma Model, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
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- Citations: 2
Ethier CR, Feola A, Raykin J, et al., 2015, Modeling the Effects of Spaceflight on the Posterior Eye in VIIP, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Chang JYH, Braakman ST, Mohri Z, et al., 2015, Colocalization of segmental outflow and endogenous eNOS activity in the conventional outflow pathway of mice, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Schwaner SA, Sherwood JM, Snider E, et al., 2015, Ocular Compliance in Mice, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Jones HJ, Girard MJ, White N, et al., 2015, Quantitative analysis of three-dimensional fibrillar collagen microstructure within the normal, aged and glaucomatous human optic nerve head, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 12, ISSN: 1742-5689
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- Citations: 26
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