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

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

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.

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 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.

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.

scholarly journals Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm’s Canal Endothelia

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lawrence C. S. Tam ◽  
Ester Reina-Torres ◽  
Joseph M. Sherwood ◽  
Paul S. Cassidy ◽  
Darragh E. Crosbie ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Schlemm’S Canal ◽  
Outflow Facility ◽  
Schlemm's Canal

scholarly journals Surface Engineering of FLT4-Targeted Nanocarriers Enhances Cell-Softening Glaucoma Therapy

2021 ◽  
Author(s):  
Michael P. Vincent ◽  
Trevor Stack ◽  
Amir Vahabikashi ◽  
Guorong Li ◽  
Kristin M. Perkumas ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Endothelial Cells ◽  
Targeted Drug Delivery ◽  
Surface Engineering ◽  
Vision Loss ◽  
Open Angle Glaucoma ◽  
Anterior Segment ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Targeted Drug

Primary open-angle glaucoma is associated with elevated intraocular pressure (IOP) that damages the optic nerve and leads to gradual vision loss. Several agents that reduce the stiffness of pressure-regulating Schlemm's canal endothelial cells, in the conventional outflow pathway of the eye, lower IOP in glaucoma patients and are approved for clinical use. However, poor drug penetration and uncontrolled biodistribution limit their efficacy and produce local adverse effects. Compared to other ocular endothelia, FLT4/VEGFR3 is expressed at elevated levels by Schlemm's canal endothelial cells and can be exploited for targeted drug delivery. Here, we validate FLT4 receptors as a clinically-relevant target on Schlemm's canal cells from glaucomatous human donors and engineer polymeric self-assembled nanocarriers displaying lipid-anchored targeting ligands that optimally engage this receptor. Targeting constructs were synthesized as lipid-PEGX-peptide, differing in the number of PEG spacer units (x), and were embedded in micelles. We present a novel proteolysis assay for quantifying ligand accessibility that we employ to design and optimize our FLT4-targeting strategy for glaucoma nanotherapy. Peptide accessibility to proteases correlated with receptor-mediated targeting enhancements. Increasing the accessibility of FLT4-binding peptides enhanced nanocarrier uptake by Schlemm's canal cells while simultaneously decreasing uptake by off-target vascular endothelial cells. Using a paired longitudinal IOP study in vivo, we show this enhanced targeting of Schlemm's canal cells translates to IOP reductions that are sustained for a significantly longer time as compared to controls. Histological analysis of murine anterior segment tissue confirmed nanocarrier localization to Schlemm's canal within one hour after intracameral administration. This work demonstrates that steric effects between surface-displayed ligands and PEG coronas significantly impact targeting performance of synthetic nanocarriers across multiple biological scales. Minimizing the obstruction of modular targeting ligands by PEG measurably improved the efficacy of glaucoma nanotherapy and is an important consideration for engineering PEGylated nanocarriers for targeted drug delivery.

scholarly journals siRNA targeting Schlemm’s canal endothelial tight junctions enhances outflow facility and reduces IOP in a steroid-induced OHT rodent model

2021 ◽  
Vol 20 ◽  
pp. 86-94
Author(s):  
Paul S. Cassidy ◽  
Ruth A. Kelly ◽  
Ester Reina-Torres ◽  
Joseph M. Sherwood ◽  
Marian M. Humphries ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Rodent Model ◽  
Schlemm’S Canal ◽  
Outflow Facility ◽  
Schlemm's Canal
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