Document Detail


Interferon-γ regulates discordant mechanisms of uveitis versus joint and axial disease in a murine model resembling spondylarthritis.
MedLine Citation:
PMID:  21987263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The spondylarthritides (such as ankylosing spondylitis) are multisystem inflammatory diseases that frequently result in uveitis. Despite the common co-occurrence of uveitis with arthritis, there has been no explanation for the susceptibility of the eye to inflammation. Using an innovative intravital videomicroscopic approach, we discovered the coexistence of uveitis with axial and peripheral joint inflammation in mice immunized with cartilage proteoglycan (PG). The aim of this study was to elucidate the characteristics of uveitis and test the impact of interferon-γ (IFNγ) deficiency on the eye versus the joint and spine.
METHODS: Female T cell receptor (TCR)-transgenic mice or IFNγ-knockout mice crossed to TCR-transgenic mice were immunized with PG. Uveitis was assessed by intravital videomicroscopy and histology. The clinical and histopathologic severity of arthritis and spondylitis were evaluated. The bone remodeling process within the spine was assessed by whole-body near-infrared imaging. Immunoblotting and immunofluorescence staining were used to examine the expression of PG and ADAMTS-5 and to examine the cellular composition of eyes with uveitis.
RESULTS: PG neoepitopes along with the aggrecanase ADAMTS-5 were present in the eye, as they were the joint. Anterior uveitis developed in response to PG immunization. The cellular infiltrate consisted mainly of neutrophils and eosinophils. Unexpectedly, IFNγ deficiency markedly exacerbated uveitis while ameliorating joint and spine disease, indicating divergent mechanisms that drive diseases in the eye versus the joints and spine.
CONCLUSION: This study provides the first detailed description of a murine disease model in which uveitis coincides with arthritis and spondylitis. Our observations provide a great opportunity for understanding the pathogenesis of a relatively common but poorly understood disease.
Authors:
Jelena M Kezic; Michael P Davey; Tibor T Glant; James T Rosenbaum; Holly L Rosenzweig
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  64     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-29     Completed Date:  2012-07-10     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  762-71     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / metabolism
Aggrecans / immunology,  metabolism,  pharmacology
Animals
Cartilage / immunology,  metabolism
Disease Models, Animal
Epitopes
Eye / metabolism,  pathology
Female
Interferon-gamma / metabolism*
Mice
Mice, Inbred BALB C
Mice, Knockout
Spondylarthritis / immunology,  metabolism,  pathology*
Uveitis, Anterior / immunology,  metabolism,  pathology*
Grant Support
ID/Acronym/Agency:
EY-019020/EY/NEI NIH HHS; EY-019604/EY/NEI NIH HHS; EY-021733/EY/NEI NIH HHS; P30 EY010572/EY/NEI NIH HHS; R01 AR040310/AR/NIAMS NIH HHS; R01 AR059356/AR/NIAMS NIH HHS; R01 EY019020/EY/NEI NIH HHS; R01 EY019020-01A1/EY/NEI NIH HHS; R01 EY019604/EY/NEI NIH HHS; R01 EY019604-01/EY/NEI NIH HHS; R01 EY021733/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Aggrecans; 0/Epitopes; 82115-62-6/Interferon-gamma; EC 3.4.24.-/ADAM Proteins
Comments/Corrections

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


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