Rho GTPase-mediated cytoskeletal organization in Schlemm's canal cells play a critical role in the regulation of aqueous humor outflow facility

2011 ◽  
Vol 112 (2) ◽  
pp. 600-606 ◽  
Author(s):  
Janardan Kumar ◽  
David L. Epstein
Keyword(s):  
Aqueous Humor ◽  
Rho Gtpase ◽  
Critical Role ◽  
Schlemm’S Canal ◽  
Cytoskeletal Organization ◽  
Outflow Facility ◽  
Aqueous Humor Outflow ◽  
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 An imaged-based inverse finite element method to determine in-vivo mechanical properties of the human trabecular meshwork

2017 ◽  
Vol 1 (3) ◽  
pp. 100-111
Author(s):  
Anup D. Pant ◽  
Larry Kagemann ◽  
Joel S. Schuman ◽  
Ian A. Sigal ◽  
Rouzbeh Amini
Keyword(s):  
Mechanical Properties ◽  
Finite Element ◽  
Shear Modulus ◽  
Trabecular Meshwork ◽  
Computational Simulation ◽  
Optimization Technique ◽  
Schlemm’S Canal ◽  
Aqueous Humor Outflow ◽  
Schlemm's Canal

Aim/Purpose: Previous studies have shown that the trabecular meshwork (TM) is mechanically stiffer in glaucomatous eyes as compared to normal eyes. It is believed that elevated TM stiffness increases resistance to the aqueous humor outflow, producing increased intraocular pressure (IOP).It would be advantageous to measure TM mechanical properties in vivo, as these properties are believed to play an important role in the pathophysiology of glaucoma and could be useful for identifying potential risk factors.  The purpose of this study was to develop a method to estimate in-vivo TM mechanical properties using clinically available exams and computer simulations.Design: Inverse finite element simulationMethods: A finite element model of the TM was constructed from optical coherence tomography (OCT) images of a healthy volunteer before and during IOP elevation. An axisymmetric model of the TM was then constructed. Images of the TM at a baseline IOP level of 11, and elevated level of 23 mmHg were treated as the undeformed and deformed configurations, respectively. An inverse modeling technique was subsequently used to estimate the TM shear modulus (G). An optimization technique was used to find the shear modulus that minimized the difference between Schlemm’s canal area in the in-vivo images and simulations.Results: Upon completion of inverse finite element modeling, the simulated area of the Schlemm’s canal changed from 8,889 μm2 to 2,088 μm2, similar to the experimentally measured areal change of the canal (from 8,889 μm2 to 2,100 μm2). The calculated value of shear modulus was found to be 1.93 kPa,  (implying an approximate Young’s modulus of 5.75 kPa), which is consistent with previous ex-vivo measurements.Conclusion: The combined imaging and computational simulation technique provides a unique approach to calculate the mechanical properties of the TM in vivo without any surgical intervention. Quantification of such mechanical properties will help us examine the mechanistic role of TM biomechanics in the regulation of IOP in healthy and glaucomatous eyes. 

5-Methylurapidil, 8-Iso Prostaglandin E2: New Drugs to Increase Aqueous-Humor Outflow Facility

2000 ◽  
pp. 253-259
Author(s):  
J. B. Serle ◽  
S. M. Podos ◽  
R.-F. Wang ◽  
T. Mittag ◽  
P.-Y. Lee ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Aqueous Humor ◽  
New Drugs ◽  
Outflow Facility ◽  
Aqueous Humor Outflow

Role of Lysophospholipid Growth Factors in the Modulation of Aqueous Humor Outflow Facility

2004 ◽  
Vol 45 (7) ◽  
pp. 2263 ◽  
Author(s):  
Priyatham Sai Mettu ◽  
Pei-Feng Deng ◽  
Uma K. Misra ◽  
Govind Gawdi ◽  
David L. Epstein ◽  
...  
Keyword(s):  
Growth Factors ◽  
Aqueous Humor ◽  
Outflow Facility ◽  
Aqueous Humor Outflow

scholarly journals Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation

2020 ◽  
Vol 6 (18) ◽  
pp. eaay8699
Author(s):  
Philipp P. Prosseda ◽  
Jorge A. Alvarado ◽  
Biao Wang ◽  
Tia J. Kowal ◽  
Ke Ning ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Primary Cilia ◽  
Vision Loss ◽  
Critical Role ◽  
Calcium Dependent ◽  
Aqueous Humor Outflow ◽  
Trabecular Meshwork Cells ◽  
Eye Pressure ◽  
Stimulation Of

Glaucoma is a group of progressive optic neuropathies that cause irreversible vision loss. Although elevated intraocular pressure (IOP) is associated with the development and progression of glaucoma, the mechanisms for its regulation are not well understood. Here, we have designed CIBN/CRY2-based optogenetic constructs to study phosphoinositide regulation within distinct subcellular compartments. We show that stimulation of CRY2-OCRL, an inositol 5-phosphatase, increases aqueous humor outflow and lowers IOP in vivo, which is caused by a calcium-dependent actin rearrangement of the trabecular meshwork cells. Phosphoinositide stimulation also rescues defective aqueous outflow and IOP in a Lowe syndrome mouse model but not in IFT88fl/fl mice that lack functional cilia. Thus, our study is the first to use optogenetics to regulate eye pressure and demonstrate that tight regulation of phosphoinositides is critical for aqueous humor homeostasis in both normal and diseased eyes.

The role of protein kinase C in modulation of aqueous humor outflow facility

2003 ◽  
Vol 76 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Rahul N Khurana ◽  
Pei-Feng Deng ◽  
David L Epstein ◽  
P Vasantha Rao
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Aqueous Humor ◽  
Outflow Facility ◽  
Aqueous Humor Outflow ◽  
Kinase C

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 Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0161332 ◽  
Author(s):  
Tomokazu Fujimoto ◽  
Toshihiro Inoue ◽  
Kei Maki ◽  
Miyuki Inoue-Mochita ◽  
Hidenobu Tanihara
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Aqueous Humor ◽  
Vascular Endothelial ◽  
Outflow Facility ◽  
Aqueous Humor Outflow ◽  
Endothelial Growth Factor
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