IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2005;46:823-832.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0549
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kenney, M. C.
Right arrow Articles by Brown, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kenney, M. C.
Right arrow Articles by Brown, D. J.

Increased Levels of Catalase and Cathepsin V/L2 but Decreased TIMP-1 in Keratoconus Corneas: Evidence that Oxidative Stress Plays a Role in This Disorder

M. Cristina Kenney,1,2 Marilyn Chwa,1 Shari R. Atilano,1 Annie Tran,1 Marilee Carballo,1 Mehrnoosh Saghizadeh,3 Vasilis Vasiliou,4 Wakako Adachi,5 and Donald J. Brown1

1From the Department of Ophthalmology, University of California Irvine, Medical Center, Irvine, California; the 3Jules Stein Eye Institute, University of California at Los Angeles, Los Angeles, California; 4Molecular Toxicology and Environmental Health Sciences Program, University of Colorado Health Sciences Center, Denver, Colorado; the 5Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; and 2Cedars-Sinai Medical Center, Los Angeles, California.

PURPOSE. The mRNA levels of antioxidant enzymes, matrix metalloproteinases, cathepsin V/L2, and tissue inhibitor of matrix metalloproteinases (TIMPs) were determined in keratoconus and normal corneas. Protein levels or enzyme activities were analyzed when RNA levels were different.

METHODS. A total of 25 physiologic (normal) and 32 keratoconus corneas were studied. mRNAs were analyzed by semiquantitative reverse transcription–polymerase chain reaction and Southern blot analysis. Proteins were assessed by immunohistochemistry and/or Western blot analysis. Catalase activity was measured in corneal extracts. Antioxidant enzymes examined were catalase, superoxide dismutase (SOD)-1, SOD3, glutathione reductase, glutathione S-transferase and aldehyde dehydrogenase 3A1. Degradative enzymes examined were cathepsin V/L2 and matrix metalloproteinase (MMP)-1, -2, -7, -9, and -14. Tissue inhibitor of matrix metalloproteinase (TIMP)-1, -2, and -3 were also examined.

RESULTS. Keratoconus corneas exhibited a 2.2-fold increase of catalase mRNA level (P < 0.01) and 1.8-fold of enzyme activity (P < 0.03); a 1.5-fold increase of cathepsin V/L2 mRNA (P < 0.03) and abnormal protein distribution; and a 1.8-fold decrease of TIMP-1 mRNA (P < 0.05) and 2.8-fold decrease of protein (P < 0.0001) compared with normal (physiologic) corneas. RNA levels for other antioxidant and degradative enzymes were similar between normal and keratoconus corneas.

CONCLUSIONS. Keratoconus corneas have elevated levels of cathepsins V/L2, -B, and -G, which can stimulate hydrogen peroxide production, which, in turn, can upregulate catalase, an antioxidant enzyme. In addition, decreased TIMP-1 and increased cathepsin V/L2 levels may play a role in the matrix degradation that is a hallmark of keratoconus corneas. The findings support the hypothesis that keratoconus corneas undergo oxidative stress and tissue degradation.




This article has been cited by other articles:


Home page
 IOVSHome page
H. C. Turner, M. T. Budak, M. A. M. Akinci, and J. M. Wolosin
Comparative Analysis of Human Conjunctival and Corneal Epithelial Gene Expression with Oligonucleotide Microarrays
Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2050 - 2061.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. H.-K. Ma, J.-Y. Yao, M.-T. Kuo, L.-C. See, K.-Y. Lin, S.-C. Chen, J.-K. Chen, A.-S. Chao, S.-F. Wang, and K.-K. Lin
Generation of Endostatin by Matrix Metalloproteinase and Cathepsin from Human Limbocorneal Epithelial Cells Cultivated on Amniotic Membrane
Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 644 - 651.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
N. Udar, S. R. Atilano, D. J. Brown, B. Holguin, K. Small, A. B. Nesburn, and M. C. Kenney
SOD1: A Candidate Gene for Keratoconus.
Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3345 - 3351.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
M. Chwa, S. R. Atilano, V. Reddy, N. Jordan, D. W. Kim, and M. C. Kenney
Increased Stress-Induced Generation of Reactive Oxygen Species and Apoptosis in Human Keratoconus Fibroblasts
Invest. Ophthalmol. Vis. Sci., May 1, 2006; 47(5): 1902 - 1910.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
F. Chiambaretta, H. Nakamura, F. De Graeve, H. Sakai, G. Marceau, Y. Maruyama, D. Rigal, B. Dastugue, J. Sugar, B. Y. J. T. Yue, et al.
Kruppel-like Factor 6 (KLF6) Affects the Promoter Activity of the {alpha}1-Proteinase Inhibitor Gene
Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 582 - 590.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. R. Atilano, P. Coskun, M. Chwa, N. Jordan, V. Reddy, K. Le, D. C. Wallace, and M. C. Kenney
Accumulation of Mitochondrial DNA Damage in Keratoconus Corneas
Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1256 - 1263.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the Association for Research in Vision and Ophthalmology