Document Detail


Proinflammatory cytokines are involved in the initiation of the abnormal matrix process in pseudoexfoliation syndrome/glaucoma.
MedLine Citation:
PMID:  20395431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pseudoexfoliation (PEX) syndrome, which is an age-related, generalized elastotic matrix process, currently represents the most common identifiable risk factor for open-angle glaucoma. Dysregulated expression of proinflammatory cytokines has been implicated in the initiation of various fibrotic disorders and in the pathophysiology of glaucoma. Here we investigated the presence, expression, regulation, and functional significance of proinflammatory cytokines in eyes with early and late stages of PEX syndrome/glaucoma in comparison with normal and glaucomatous control eyes using multiplex bead analysis, immunoassays, real-time PCR, Western blotting, immunohistochemistry, and cell culture models. Early stages of PEX syndrome were characterized by approximately threefold (P < 0.005) elevated interleukin (IL)-6 and IL-8 levels in the aqueous humor and a concomitant approximately twofold (P < 0.001) increase in mRNA expression levels in anterior segment tissues as compared with controls. In contrast, late stages of PEX syndrome/glaucoma did not differ significantly from controls. IL-6, IL-6 receptor, and phospho-signal transducer and activator of transcription 3 could be mainly localized to walls of iris vessels and to the nonpigmented epithelium of ciliary processes. IL-6 and IL-8 were significantly up-regulated by ciliary epithelial cells in response to hypoxia or oxidative stress in vitro, whereas IL-6, but not IL-8, induced the expression of transforming growth factor-beta1 and elastic fiber proteins. These findings support a role for a stress-induced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic matrix process characteristic of PEX syndrome/glaucoma.
Authors:
Matthias Zenkel; Piotr Lewczuk; Anselm Jünemann; Friedrich E Kruse; Gottfried O H Naumann; Ursula Schlötzer-Schrehardt
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-15
Journal Detail:
Title:  The American journal of pathology     Volume:  176     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-03     Completed Date:  2010-10-04     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2868-79     Citation Subset:  AIM; IM    
Affiliation:
Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6, D-91054 Erlangen, Germany. matthias.zenkel@uk-erlangen.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Animals
Aqueous Humor / immunology
Cell Line
Cytokines / genetics,  immunology*
Exfoliation Syndrome* / immunology,  pathology,  physiopathology
Extracellular Matrix / metabolism,  pathology*
Eye / anatomy & histology,  immunology,  pathology,  physiopathology
Female
Glaucoma, Open-Angle* / immunology,  pathology,  physiopathology
Humans
Interleukin-6 / genetics,  immunology
Interleukin-8 / genetics,  immunology
Male
Middle Aged
Molecular Sequence Data
Chemical
Reg. No./Substance:
0/Cytokines; 0/Interleukin-6; 0/Interleukin-8
Comments/Corrections

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