scholarly journals Expression Profiling of Human Schlemm's Canal Endothelial Cells From Eyes With and Without Glaucoma

2015 ◽  
Vol 56 (11) ◽  
pp. 6747 ◽  
Author(s):  
Jingwen Cai ◽  
Kristin M. Perkumas ◽  
Xuejun Qin ◽  
Michael A. Hauser ◽  
W. Daniel Stamer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Expression Profiling ◽  
Schlemm’S Canal ◽  
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 Young’s modulus of elasticity of Schlemm’s canal endothelial cells

2009 ◽  
Vol 9 (1) ◽  
pp. 19-33 ◽  
Author(s):  
Dehong Zeng ◽  
Taras Juzkiw ◽  
A. Thomas Read ◽  
Darren W.-H. Chan ◽  
Matthew R. Glucksberg ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Young’S Modulus ◽  
Modulus Of Elasticity ◽  
Young's Modulus ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Young’S Modulus Of Elasticity

scholarly journals Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells

2014 ◽  
Vol 127 ◽  
pp. 224-235 ◽  
Author(s):  
Sietse T. Braakman ◽  
Ryan M. Pedrigi ◽  
A. Thomas Read ◽  
James A.E. Smith ◽  
W. Daniel Stamer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pore Formation ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Biomechanical Strain

scholarly journals Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma

Small ◽  
2020 ◽  
Vol 16 (43) ◽  
pp. 2004205
Author(s):  
Trevor Stack ◽  
Michael Vincent ◽  
Amir Vahabikashi ◽  
Guorong Li ◽  
Kristin M. Perkumas ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Targeted Delivery ◽  
Schlemm’S Canal ◽  
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 Biomechanics of Schlemm's Canal Endothelial Cells: Influence on F-Actin Architecture

2004 ◽  
Vol 87 (4) ◽  
pp. 2828-2837 ◽  
Author(s):  
C. Ross Ethier ◽  
A. Thomas Read ◽  
Darren Chan
Keyword(s):  
Endothelial Cells ◽  
Schlemm’S Canal ◽  
Schlemm's Canal

The role of plasmalemma vesicle-associated protein (PLVAP) in endothelial cells of Schlemm's canal and ocular capillaries

2012 ◽  
Vol 105 ◽  
pp. 27-33 ◽  
Author(s):  
Leonie Herrnberger ◽  
Kathrin Ebner ◽  
Benjamin Junglas ◽  
Ernst R. Tamm
Keyword(s):  
Endothelial Cells ◽  
Schlemm’S Canal ◽  
Schlemm's Canal
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