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

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 Sphingosine-1-phosphate effects on the inner wall of Schlemm's canal and outflow facility in perfused human eyes

2009 ◽  
Vol 89 (6) ◽  
pp. 980-988 ◽  
Author(s):  
W. Daniel Stamer ◽  
A. Thomas Read ◽  
Grant M. Sumida ◽  
C. Ross Ethier
Keyword(s):  
Schlemm’S Canal ◽  
Outflow Facility ◽  
Schlemm's Canal ◽  
Sphingosine 1 Phosphate ◽  
Human Eyes

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 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 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

scholarly journals Increased stiffness and flow resistance of the inner wall of Schlemm’s canal in glaucomatous human eyes

2019 ◽  
Vol 116 (52) ◽  
pp. 26555-26563 ◽  
Author(s):  
Amir Vahabikashi ◽  
Ariel Gelman ◽  
Biqin Dong ◽  
Lihua Gong ◽  
Elliott D. K. Cha ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Flow Resistance ◽  
Tissue Stiffness ◽  
Schlemm’S Canal ◽  
Force Microscopy ◽  
Schlemm's Canal ◽  
Afm Indentation ◽  
Atomic Force ◽  
Tissue Surface ◽  
Human Eyes

The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the stiffness of the inner wall of Schlemm’s canal as a function of distance from the tissue surface in normal and glaucomatous postmortem human eyes, and 1-µm spherical AFM tips to probe the region immediately below the tissue surface. To localize flow resistance, perfusion and imaging methods were used to characterize the pressure drop in the immediate vicinity of the inner wall using giant vacuoles that form in Schlemm’s canal cells as micropressure sensors. Tissue stiffness increased with increasing AFM indentation depth. Tissues from glaucomatous eyes were stiffer compared with normal eyes, with greatly increased stiffness residing within ∼1 µm of the inner-wall surface. Giant vacuole size and density were similar in normal and glaucomatous eyes despite lower flow rate through the latter due to their higher flow resistance. This implied that the elevated flow resistance found in the glaucomatous eyes was localized to the same region as the increased tissue stiffness. Our findings implicate pathological changes to biophysical characteristics of Schlemm’s canal endothelia and/or their immediate underlying extracellular matrix as cause for ocular hypertension in glaucoma.

Effects of viscoelastic injection into Schlemm’s canal in primate and human eyes

Ophthalmology ◽  
2002 ◽  
Vol 109 (4) ◽  
pp. 786-792 ◽  
Author(s):  
Barbara A Smit ◽  
Murray A Johnstone
Keyword(s):  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Human Eyes

scholarly journals Effects of Schlemm’s Canal Expansion: Biomechanics and MIGS Implications

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 176
Author(s):  
Chen Xin ◽  
Shaozhen Song ◽  
Ningli Wang ◽  
Ruikang Wang ◽  
Murray Johnstone
Keyword(s):  
Three Dimensional ◽  
Glaucoma Surgery ◽  
Pressure Control ◽  
Biomechanical Properties ◽  
Schlemm’S Canal ◽  
Fluid Bolus ◽  
Cross Sectional ◽  
Schlemm's Canal ◽  
Anterior Segments ◽  
The Right

Objective: To evaluate the change of biomechanical properties of the trabecular meshwork (TM) and configuration of collector channels (CC) by high-resolution optical coherence tomography (HR-OCT) induced by Schlemm’s canal (SC) dilation. Methods: The anterior segments of two human eyes were divided into four quadrants. One end of a specially designed cannula was placed in SC and the other end connected to a perfusion reservoir. HR-OCT provided three-dimensional (3D) volumetric and two-dimensional (2D) cross-sectional imaging permitting assessment of the biomechanical properties of the TM. A large fluid bolus was introduced into SC. Same-sample, pre and post deformation and disruption of SC and CC lumen areas were analyzed. Results: Morphologic 3D reconstructions documented pressure-dependent changes in lumen dimension of SC, CC, and circumferential intrascleral channels. 2D imaging established volumetric stress-strain curves (elastance curves) of the TM in quadrants. The curves of TM elastance shift to the right with an increase in pressure-dependent steady-state SC area. After a bolus disruption, the SC area increased, while the CC area decreased. Conclusion: Our experimental setup permits the study of the biomechanical properties of TM by examining elastance, which differs segmentally and is altered by mechanical expansion of SC by a fluid bolus. The study may shed light on mechanisms of intraocular pressure control of some glaucoma surgery.

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