Document Detail


Rho GTPase-mediated cytoskeletal organization in Schlemm's canal cells play a critical role in the regulation of aqueous humor outflow facility.
MedLine Citation:
PMID:  21268081     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The increased intraocular pressure (IOP) has been considered to be an increased resistance of the aqueous humor outflow through the inner wall of Schlemm's canal (SC) and/or the juxtacanalicular tissue (JCT). The Rho GTPase-regulated actomyosin organization appears to be an important mechanistic determinant of aqueous humor outflow facility. Therefore, in this study, we have evaluated the effects of modulating Rho GTPase activity on actomyosin cytoskeletal organization, monolayer permeability/barrier function of human SC cells, and aqueous humor outflow facility in enucleated porcine eyes ex vivo. Human SC cells, isolated from cadaver eyes, were treated with either Rho GTPase activators such as thrombin and lysophosphatidic acid (LPA), or a specific inhibitor (C3-exoenzyme) of Rho GTPases. Treatment of SC cells with thrombin and LPA led to increased formation of stress fibers, focal adhesion, and increased myosin light chain phosphorylation, whereas treatment with C3-exoenzyme showed the opposite effects like H-7 and ECA, known for increasing the outflow facility in porcine eyes. The findings presented here suggest that LPA and thrombin, presumably through activation of Rho GTPase-mediated actomyosin cytoskeletal reorganization in SC cells, cause a decrease in monolayer permeability of SC cells as well as a decrease in outflow facility of porcine eyes in ex vivo. Our results suggest that decrease in aqueous humor outflow may be correlated better with the changes in cytoskeletal organizations of SC, which could be the prime locus of the outflow resistance.
Authors:
Janardan Kumar; David L Epstein
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  112     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-05-03     Revised Date:  2013-05-02    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  600-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
Affiliation:
Department of Natural Sciences, Becker College, Worcester, Massachusetts 01609, USA. janardan.kumar@becker.edu
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Aqueous Humor / cytology*,  physiology
Cells, Cultured
Cytoskeleton / metabolism*
Endothelial Cells / metabolism*
Focal Adhesions / metabolism
Humans
Myosin Light Chains / metabolism
Phosphorylation
Thrombin / metabolism
rho GTP-Binding Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
R01 EY001894/EY/NEI NIH HHS; R01 EY01894/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Myosin Light Chains; EC 3.4.21.5/Thrombin; EC 3.6.5.2/rho GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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