scholarly journals Pharmacological regulation of outflow resistance distal to Schlemm’s canal

2018 ◽  
Vol 315 (1) ◽  
pp. C44-C51 ◽  
Author(s):  
Fiona McDonnell ◽  
W. Michael Dismuke ◽  
Darryl R. Overby ◽  
W. Daniel Stamer
Keyword(s):  
Dynamic Range ◽  
Smooth Muscle Actin ◽  
Anterior Segment ◽  
Physiological Model ◽  
Outflow Resistance ◽  
Schlemm’S Canal ◽  
Outflow Facility ◽  
Schlemm's Canal ◽  
Anterior Segments ◽  
Outflow Pathway

The trabecular meshwork (TM) and Schlemm’s canal generate the majority of outflow resistance; however, the distal regions of the conventional outflow pathway account for 25–50% of total resistance. Sections of distal vessels are surrounded by α-smooth muscle actin-containing cells, indicating that they may be vasoregulated. This study examined the effect of a potent vasodilator, nitric oxide (NO), and its physiological antagonist, endothelin-1 (ET-1), on the regulation of outflow resistance in the distal regions of the conventional outflow pathway. Using a physiological model of the conventional outflow pathway, human and porcine anterior segments were perfused in organ culture under constant flow conditions, while intrachamber pressure was continually monitored. For porcine anterior segments, a stable baseline outflow facility with TM intact was first achieved before anterior segments were removed and a trabeculotomy was performed. For human anterior segments, a trabeculotomy was immediately performed. In human anterior segments, 100 nM ET-1 significantly decreased distal outflow facility from 0.49 ± 0.26 to 0.31 ±  0.18 (mean ± SD) µl·min−1·mmHg, P < 0.01. Perfusion with 100 µM diethylenetriamine-NO in the presence of 1 nM ET-1 immediately reversed ET-1 effects, significantly increasing distal outflow facility to 0.54 ± 0.35 µl·min−1·mmHg, P = 0.01. Similar results were obtained in porcine anterior segment experiments. Therefore, data show a dynamic range of resistance generation by distal vessels in both the human and the porcine conventional outflow pathways. Interestingly, maximal contraction of vessels in the distal outflow tract of trabeculotomized eyes generated resistance very near physiological levels for both species having an intact TM.

A Novel 8-mm Schlemm's Canal Scaffold Reduces Outflow Resistance in a Human Anterior Segment Perfusion Model

2013 ◽  
Vol 54 (3) ◽  
pp. 1698 ◽  
Author(s):  
Vikas Gulati ◽  
Shan Fan ◽  
Cassandra L. Hays ◽  
Thomas W. Samuelson ◽  
Iqbal Ike K. Ahmed ◽  
...  
Keyword(s):  
Anterior Segment ◽  
Outflow Resistance ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Perfusion Model

Pharmacologic Disruption of Schlemm’s Canal Cells and Outflow Facility in Anterior Segments of Human Eyes

2004 ◽  
Vol 45 (7) ◽  
pp. 2246 ◽  
Author(s):  
Cindy K. Bahler ◽  
Cheryl R. Hann ◽  
Michael P. Fautsch ◽  
Douglas H. Johnson
Keyword(s):  
Schlemm’S Canal ◽  
Outflow Facility ◽  
Schlemm's Canal ◽  
Anterior Segments ◽  
Human Eyes

A Novel Schlemm's Canal Scaffold Increases Outflow Facility in a Human Anterior Segment Perfusion Model

2012 ◽  
Vol 53 (10) ◽  
pp. 6115 ◽  
Author(s):  
Lucinda J. Camras ◽  
Fan Yuan ◽  
Shan Fan ◽  
Thomas W. Samuelson ◽  
Ike K. Ahmed ◽  
...  
Keyword(s):  
Anterior Segment ◽  
Schlemm’S Canal ◽  
Outflow Facility ◽  
Schlemm's Canal ◽  
Perfusion Model

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 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.

Trabecular Bypass: Effect of Schlemm’s Canal and Collector Channel Dilation

2004 ◽  
Author(s):  
Jianbo Zhou ◽  
Gregory T. Smedley
Keyword(s):  
Intraocular Pressure ◽  
Second Order ◽  
Polynomial Equations ◽  
Outflow Resistance ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Elevated Intraocular Pressure ◽  
Order Polynomial ◽  
Trabecular Bypass

An ocular outflow model is proposed to theorize the effect of Schlemm’s canal (SC) and/or collector channel (CC) dilation combined with a trabecular bypass on elevated intraocular pressure (IOP) in glaucomatous eyes. The dilated height of the elliptic SC is largest at the bypass and linearly deceases to the non-dilated height over the dilated circumferential length. The CC dilation is modeled with a reduced outflow resistance of second order polynomial. Equations governing the pressure and flow in SC are solved numerically. The model predicts that the IOP is reduced substantially with moderate dilation from the normal 20 μm to 40 μm at the bypass. SC dilation is more effective for eyes with smaller SC. The dilation of CC can also significantly lower the IOP. With the trabecular bypass alone, the elevated IOP is expected to drop to the mid-to-high teens. The IOP can be further reduced by another 3 to 6 mmHg with moderate SC and CC dilation.

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.

scholarly journals Suture Distension of Schlemm’s Canal in Canaloplasty: An Anterior Segment Imaging Study

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Livia M. Brandao ◽  
Andreas Schötzau ◽  
Matthias C. Grieshaber
Keyword(s):  
Intraocular Pressure ◽  
Anterior Segment ◽  
Imaging Study ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Anterior Segment Imaging ◽  
The Difference ◽  
Cup To Disc Ratio

Purpose. The object of this study was to investigate the role of the suture stent regarding its impact on reduction of intraocular pressure (IOP) in canaloplasty based on the distension of the inner wall of Schlemm’s canal.Methods. Nineteen glaucoma patients who underwent canaloplasty with successful positioning of the tensioning suture were included. The measurements were analyzed using linear mixed models, with the means adjusted to IOP, age, cup-to-disc ratio, and time of follow-up.Results. Mean follow-up time was 27.6 months (SD 10.5). Mean intraocular pressure (IOP) was 24.6 mmHg (SD 5.29), 13.8 (SD 2.65), and 14.5 (SD 0.71) before surgery, at 12 months, and at 36 months after surgery, respectively. 57.9% of patients had no medication at last evaluation. Differences and variations of measurements between the devices over a time of 12 months were not significant (p= 0.15 to 0.98). Some angles of distension associated with the suture stent inside SC were predictive for IOP reduction (p< 0.03 to < 0.001), but not for final IOP (p= 0.64 to 0.96).Conclusion. The angles of the inner wall of Schlemm’s canal generated by the suture stent were comparable between OCT and UBM and did not change significantly over time. There was a tendency towards a greater distension of Schlemm’s canal, when the difference was larger between pre- and postoperative IOP, suggesting the tensioning suture may contribute to IOP reduction.

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