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Overexpression of SPARC in human trabecular meshwork increases intraocular pressure and alters extracellular matrix

Title
Overexpression of SPARC in human trabecular meshwork increases intraocular pressure and alters extracellular matrix
Authors
Oh D.-J.Kang M.H.Ooi Y.H.Choi K.R.Sage E.H.Rhee D.J.
Ewha Authors
최규룡
SCOPUS Author ID
최규룡scopus
Issue Date
2013
Journal Title
Investigative Ophthalmology and Visual Science
ISSN
0146-0404JCR Link
Citation
vol. 54, no. 5, pp. 3309 - 3319
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
PURPOSE. Intraocular pressure (IOP) regulation is largely unknown. SPARC-null mice demonstrate a lower IOP resulting from increased outflow. SPARC is a matricellular protein often associated with fibrosis. We hypothesized that SPARC overexpression would alter IOP by affecting extracellular matrix (ECM) synthesis and/or turnover in the trabecular meshwork (TM). METHODS. An adenoviral vector containing human SPARC was used to increase SPARC expression in human TM endothelial cells and perfused human anterior segments using multiplicities of infection (MOIs) 25 or 50. Total RNA from TM was used for quantitative PCR, while protein from cell lysates and conditioned media were used for immunoblot analyses and zymography. After completion of perfusion, the anterior segments were fixed, sectioned, and examined by light and confocal microscopy. RESULTS. SPARC overexpression increased the IOP of perfused human anterior segments. Fibronectin and collagens IV and I protein levels were elevated in both TM cell cultures and within the juxtacanalicular (JCT) region of perfused anterior segments. Collagen VI and laminin protein levels were increased in TM cell cultures but not in perfused anterior segments. The protein levels of pro-MMP-9 decreased while the kinetic inhibitors of metalloproteinases, TIMP-1 and PAI-1 protein levels, increased at MOI 25. At MOI 50, the protein levels of pro-MMP-1, -3, and -9 also decreased while PAI-1 and TIMP-1 and -3 increased. Only MMP-9 activity was decreased on zymography. mRNA levels of the collagens, fibronectin, and laminin were not affected by SPARC overexpression. CONCLUSIONS. SPARC overexpression increases IOP in perfused cadaveric human anterior segments resulting from a qualitative change the JCT ECM. Selective decrease of MMP-9 activity is likely part of the mechanism. SPARC is a regulatory node for IOP. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
DOI
10.1167/iovs.12-11362
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의학전문대학원 > 의학과 > Journal papers
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