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 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 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

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 Outflow Facility Effects of 3 Schlemm’s Canal Microinvasive Glaucoma Surgery Devices

2020 ◽  
Vol 3 (2) ◽  
pp. 114-121
Author(s):  
Carol B. Toris ◽  
Padmanabhan P. Pattabiraman ◽  
George Tye ◽  
Thomas W. Samuelson ◽  
Douglas J. Rhee
Keyword(s):  
Glaucoma Surgery ◽  
Schlemm’S Canal ◽  
Outflow Facility ◽  
Schlemm's Canal
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