scholarly journals An imaged-based inverse finite element method to determine in-vivo mechanical properties of the human trabecular meshwork

2017 ◽  
Vol 1 (3) ◽  
pp. 100-111
Author(s):  
Anup D. Pant ◽  
Larry Kagemann ◽  
Joel S. Schuman ◽  
Ian A. Sigal ◽  
Rouzbeh Amini
Keyword(s):  
Mechanical Properties ◽  
Finite Element ◽  
Shear Modulus ◽  
Trabecular Meshwork ◽  
Computational Simulation ◽  
Optimization Technique ◽  
Schlemm’S Canal ◽  
Aqueous Humor Outflow ◽  
Schlemm's Canal

Aim/Purpose: Previous studies have shown that the trabecular meshwork (TM) is mechanically stiffer in glaucomatous eyes as compared to normal eyes. It is believed that elevated TM stiffness increases resistance to the aqueous humor outflow, producing increased intraocular pressure (IOP).It would be advantageous to measure TM mechanical properties in vivo, as these properties are believed to play an important role in the pathophysiology of glaucoma and could be useful for identifying potential risk factors.  The purpose of this study was to develop a method to estimate in-vivo TM mechanical properties using clinically available exams and computer simulations.Design: Inverse finite element simulationMethods: A finite element model of the TM was constructed from optical coherence tomography (OCT) images of a healthy volunteer before and during IOP elevation. An axisymmetric model of the TM was then constructed. Images of the TM at a baseline IOP level of 11, and elevated level of 23 mmHg were treated as the undeformed and deformed configurations, respectively. An inverse modeling technique was subsequently used to estimate the TM shear modulus (G). An optimization technique was used to find the shear modulus that minimized the difference between Schlemm’s canal area in the in-vivo images and simulations.Results: Upon completion of inverse finite element modeling, the simulated area of the Schlemm’s canal changed from 8,889 μm2 to 2,088 μm2, similar to the experimentally measured areal change of the canal (from 8,889 μm2 to 2,100 μm2). The calculated value of shear modulus was found to be 1.93 kPa,  (implying an approximate Young’s modulus of 5.75 kPa), which is consistent with previous ex-vivo measurements.Conclusion: The combined imaging and computational simulation technique provides a unique approach to calculate the mechanical properties of the TM in vivo without any surgical intervention. Quantification of such mechanical properties will help us examine the mechanistic role of TM biomechanics in the regulation of IOP in healthy and glaucomatous eyes. 

scholarly journals Anterior Segment Optical Coherence Tomography Signs of Local Dilatation Effect of a Micro-Stent on Schlemm’s Canal

2018 ◽  
Vol 10 (2) ◽  
pp. 184-187
Author(s):  
Kevin Gillmann ◽  
Giorgio Enrico Bravetti ◽  
Kaweh Mansouri ◽  
André Mermoud
Keyword(s):  
Optical Coherence Tomography ◽  
Trabecular Meshwork ◽  
Anterior Segment ◽  
Optical Coherence ◽  
Schlemm’S Canal ◽  
New Device ◽  
Schlemm's Canal ◽  
Canal Diameter ◽  
Trabecular Bypass

Introduction: The iStent inject® (Glaukos Corporation, CA, USA) is a relatively new device designed to be implanted ab-interno through the trabecular meshwork. This is, to the best of our knowledge, the first in-vivo description of a trabecular bypass device visualised with anterior segment optical coherence tomography (AS-OCT), and report of its structural effect on Schlemm’s canal. Case Report: A 74 year-old female patient suffering from long-standing primary open-angle glaucoma and nuclear sclerosis underwent cataract surgery combined with the implantation of two iStent injects®. Surgery was uncomplicated and achieved intraocular pressure (-1 mmHg) and medication (-2 molecules) reduction at 6 months. Under AS-OCT (Spectralis OCT, Heidelberg Engineering AG, Germany) the stent appears as a 300 μm long hyper reflective hollow device within the trabecular meshwork. Approximately a third of it protruded into the anterior chamber. Profound OCT signal loss was notable within the shadow of the device. A second AS-OCT section 500 μm beside the microstent shows a markedly dilated Schlemm’s canal, with a major diameter of 390 μm. Discussions: This report confirms that AS-OCT is a suitable technique to assess microstent positioning, and provides a first report on the in-vivo appearance of a functioning stent. It also indicates that iStent injects® could have a tangible effect on adjacent portions of Schlemm’s canal with, in this case, a 220% increase in canal diameter compared to the observed average (122 μm). This suggests the IOP-lowering effect of trabecular bypass devices could rely on a  dual mechanism involving Schlemm’s canal dilatation.

Endothelia of Schlemm's canal and trabecular meshwork: distinct molecular, functional, and anatomic features

2004 ◽  
Vol 286 (3) ◽  
pp. C621-C634 ◽  
Author(s):  
Jorge A. Alvarado ◽  
Abigail Betanzos ◽  
Linda Franse-Carman ◽  
Janet Chen ◽  
Lorenza González-Mariscal
Keyword(s):  
Trabecular Meshwork ◽  
Flow Direction ◽  
Cell Types ◽  
Human Endothelial Cells ◽  
Rt Pcr ◽  
Schlemm’S Canal ◽  
Phenotypic Properties ◽  
Schlemm's Canal

The purpose of this study was to compare human endothelial cells from Schlemm's canal (SCEs) and the trabecular meshwork (TMEs) in terms of ZO-1 isoform expression, hydraulic conductivity (HC) properties, and “giant” vacuole (GV) formation. The principal study methods were Western blot, RT-PCR, immunofluorescence, and perfusion chambers. Blot signals for α+-and α--isoforms were similar in SCEs but less intense for the α+-relative to the α--signal in TMEs. With the anti-α+ antibody used at 1/50 dilution, binding occurred at cell borders of both cell types, but only to SCEs when used at a ≥1/200 dilution in vitro and in vivo. SCEs were more resistive than TMEs (HC = 0.66 vs. 1.32 μl·min-1·mmHg-1·cm-2; P < 0.001) when perfused from apex to base. When perfused in the other direction, SCEs were again more resistive (5.23 vs. 9.04 μl·min-1·mmHg-1·cm-2; P < 0.01). GV formation occurred only in SCEs as a function of flow direction, perfusion pressure, and time. We conclude that SCEs and TMEs have distinctive phenotypic properties involving their content of ZO-1 isoforms, barrier function, and GV formation.

Magnetic Resonance Elastography for the Measurement of Annulus Fibrosus Material Properties

2011 ◽  
Author(s):  
Daniel H. Cortes ◽  
Lachlan J. Smith ◽  
Sung M. Moon ◽  
Jeremy F. Magland ◽  
Alexander C. Wright ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Magnetic Resonance ◽  
Shear Modulus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Pulse Sequence ◽  
Imaging Techniques ◽  
Mechanical Vibration ◽  
Magnetic Resonance Elastography

Intervertebral disc degeneration is characterized by a progressive cascade of structural, biochemical and biomechanical changes affecting the annulus fibrosus (AF), nucleus pulposus (NP) and end plates (EP). These changes are considered to contribute to the onset of back pain. It has been shown that mechanical properties of the AF and NP change significantly with degeneration [1,2]. Therefore, mechanical properties have the potential to serve as a biomarker for diagnosis of disc degeneration. Currently, disc degeneration is diagnosed based on the detection of structural and compositional changes using MRI, X-ray, discography and other imaging techniques. These methods, however, do not measure directly the mechanical properties of the extracellular matrix of the disc. Magnetic Resonance Elastography (MRE) is a technique that has been used to measure in vivo mechanical properties of soft tissue by applying a mechanical vibration and measuring displacements with a motion-sensitized MRI pulse sequence [3]. The mechanical properties (e.g., the shear modulus) are calculated from the displacement field using an inverse method. Since the applied displacements are in the order of few microns, fibers may not be stretched enough to remove crimping. Therefore, it is unknown if the anisotropy of the AF due to the contribution of the fibers is detectable using MRE. The objective of this study is twofold: to measure shear properties of AF in different orientations to determine the degree of AF anisotropy observable by MRE, and to identify the contribution of different AF constituents to the measured shear modulus by applying different biochemical treatments.

scholarly journals Morphological changes in the trabecular meshwork and Schlemm’s canal after treatment with topical intraocular pressure-lowering agents

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji-Hye Park ◽  
Hyun Woo Chung ◽  
Eun Gyu Yoon ◽  
Min Jung Ji ◽  
Chungkwon Yoo ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Trabecular Meshwork ◽  
Morphological Changes ◽  
Open Angle Glaucoma ◽  
Anterior Segment ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Before And After ◽  
Treatment Naïve ◽  
Aqueous Outflow

AbstractGlaucoma treatment is usually initiated with topical medication that lowers the intraocular pressure (IOP) by reducing the aqueous production, enhancing the aqueous outflow, or both. However, the effect of topical IOP-lowering medications on the microstructures of the aqueous outflow pathway are relatively unknown. In this retrospective, observational study, 56 treatment-naïve patients with primary open-angle glaucoma were enrolled. Images of the nasal and temporal corneoscleral limbus were obtained using anterior segment optical coherence tomography (AS-OCT). The conjunctival vessels and iris anatomy were used as landmarks to select the same limbal area scan, and the trabecular meshwork (TM) width, TM thickness, and Schlemm’s canal (SC) area were measured before and after using the IOP-lowering agents for 3 months. Among the 56 patients enrolled, 33 patients used prostaglandin (PG) analogues, and 23 patients used dorzolamide/timolol fixed combination (DTFC). After 3 months of DTFC usage, the TM width, TM thickness, and SC area did not show significant changes in either the nasal or temporal sectors. Conversely, after prostaglandin analog usage, the TM thickness significantly increased, and the SC area significantly decreased (all P < 0.01). These findings warrant a deeper investigation into their relationship to aqueous outflow through the conventional and unconventional outflow pathways after treatment with PG analogues.

scholarly journals Schlemm's canal and trabecular meshwork morphology in high myopia

2018 ◽  
Vol 38 (3) ◽  
pp. 266-272 ◽  
Author(s):  
Zhiqi Chen ◽  
Yinwei Song ◽  
Mu Li ◽  
Wei Chen ◽  
Shiliang Liu ◽  
...  
Keyword(s):  
Trabecular Meshwork ◽  
High Myopia ◽  
Schlemm’S Canal ◽  
Schlemm's Canal

scholarly journals Effects of selective EP2 receptor agonist, omidenepag, on trabecular meshwork cells, Schlemm’s canal endothelial cells and ciliary muscle contraction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Natsuko Nakamura ◽  
Megumi Honjo ◽  
Reiko Yamagishi ◽  
Nozomi Igarashi ◽  
Rei Sakata ◽  
...  
Keyword(s):  
Trabecular Meshwork ◽  
Receptor Agonist ◽  
Ciliary Muscle ◽  
Cell Permeability ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Ep2 Receptor ◽  
Mlc Phosphorylation ◽  
Related Proteins ◽  
Outflow Pathway

AbstractThis study investigated the effects of omidenepag (OMD), a novel selective EP2 receptor agonist, on human trabecular meshwork (HTM) cells, monkey Schlemm’s canal endothelial (SCE) cells, and porcine ciliary muscle (CM) to clarify the mechanism of intraocular pressure (IOP) reduction involving conventional outflow pathway. In HTM and SCE cells, the effects of OMD on transforming growth factor-β2 (TGF-β2)-induced changes were examined. The expression of actin cytoskeleton and extracellular matrix (ECM) proteins, myosin light chain (MLC) phosphorylation in HTM cells were evaluated using real-time quantitative PCR, immunocytochemistry, and western blotting. The expression of barrier-related proteins, ZO-1 and β-catenin, and permeability of SCE cells were evaluated using immunocytochemistry and transendothelial electrical resistance. The CM contraction was determined by contractibility assay. OMD significantly inhibited expression of TGF-β2 induced mRNA, protein, and MLC-phosphorylation on cytoskeletal and ECM remodeling in the HTM dose dependently. In SCE cells, OMD suppressed TGF-β2-induced expression of the barrier-related proteins and decreased SCE monolayer permeability. OMD at 3 µM significantly inhibited CM contraction, however, the effect was not significant at lower concentrations. IOP lowering effect of OMD through conventional outflow pathway is exerted by increasing outflow facilities with the modulation of TM cell fibrosis and SCE cell permeability.

scholarly journals Role of nitric oxide in murine conventional outflow physiology

2015 ◽  
Vol 309 (4) ◽  
pp. C205-C214 ◽  
Author(s):  
Jason Y. H. Chang ◽  
W. Daniel Stamer ◽  
Jacques Bertrand ◽  
A. Thomas Read ◽  
Catherine M. Marando ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Fluorescent Protein ◽  
Detectable Effect ◽  
No Production ◽  
Schlemm’S Canal ◽  
Physiological Regulation ◽  
Outflow Facility ◽  
Aqueous Humor Outflow ◽  
Schlemm's Canal

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.

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