Document Detail

Effect of excess synthesis of extracellular matrix components by trabecular meshwork cells: possible consequence on aqueous outflow.
MedLine Citation:
PMID:  17350618     Owner:  NLM     Status:  MEDLINE    
The extracellular matrix (ECM) of the trabecular meshwork (TM) is an important determinant of its functional properties. This study was performed to investigate whether overexpression of ECM components, laminin (LM) and collagen type IV (Col) by TM cells may play a role in the development of outflow resistance. To determine the effect of excess LM and Col expression on cell monolayer permeability, an in vitro cell culture model was used in which overexpression of the two ECM components, LM and Col, was induced by high glucose (HG) (30 mM) or 0.1 microM dexamethasone (D) in bovine and human trabecular meshwork (BTM and HTM) cells. Western blot analysis and immunofluorescence staining confirmed increased LM and Col synthesis in cells exposed to HG or D. Increased level of LM and Col protein resulted in reduced cell monolayer permeability. Transfection with antisense oligos (AS-oligos) targeted against LM or Col inhibited HG- or D-induced LM and Col gene overexpression in TM cells with concomitant increase in permeability. The AS-oligo strategy was effective in reducing LM or Col level in the TM cells in all conditions tested in this study. These findings suggest that increased LM and Col deposition in the outflow pathway may cause resistance to aqueous outflow and contribute to the development of primary open angle glaucoma (POAG).
Nobuhiro Tane; Sonya Dhar; Sumon Roy; Andre Pinheiro; Akihiro Ohira; Sayon Roy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-14
Journal Detail:
Title:  Experimental eye research     Volume:  84     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-23     Completed Date:  2007-07-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  832-42     Citation Subset:  IM    
Department of Medicine, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
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MeSH Terms
Aqueous Humor / physiology*
Blotting, Western
Cells, Cultured
Collagen Type IV / biosynthesis,  genetics
Dexamethasone / pharmacology
Extracellular Matrix / metabolism
Extracellular Matrix Proteins / biosynthesis*
Gene Expression Regulation
Glucocorticoids / pharmacology
Glucose / pharmacology
Laminin / biosynthesis,  genetics
Oligoribonucleotides, Antisense / genetics
Trabecular Meshwork / cytology,  metabolism*
Reg. No./Substance:
0/Collagen Type IV; 0/Extracellular Matrix Proteins; 0/Glucocorticoids; 0/Laminin; 0/Oligoribonucleotides, Antisense; 50-02-2/Dexamethasone; 50-99-7/Glucose

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