April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Expression Analysis of Cytokine and Chemokine Genes During the Natural Course of Murine Experimental Autoimmune Uveoretinitis
Author Affiliations & Notes
  • N. Hashida
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
    Depts of Ophthalmology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland
  • S. Hohki
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • N. Ohguro
    Dept of Ophthalmology, Osaka Univ Medical School, Suita, Japan
  • Footnotes
    Commercial Relationships  N. Hashida, None; S. Hohki, None; N. Ohguro, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4822. doi:
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      N. Hashida, S. Hohki, N. Ohguro; Expression Analysis of Cytokine and Chemokine Genes During the Natural Course of Murine Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4822.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The aim of this study was to investigate sequential expression changes in cytokines and chemokines and their receptors during the natural course of murine experimental autoimmune uveoretinitis (EAU).

Methods: : C57BL/6 mice were immunized with human interphotoreceptor retinoid-binding protein peptides to induce EAU. From immunization to 30 days after immunization, RNA was isolated daily from the eyes of EAU mice. For gene expression analysis, dynamic changes in gene expression during the pathogenesis of EAU were analyzed by TaqMan Gene Expression Assay (Low Density Array) that contained most chemokines/cytokines and their receptors (96 genes), using beta-actin as the endogenous control. Data comparisons between EAU mice and normal control mice were performed. Gene clusters based on the expression profiles were analyzed to determine the candidate genes for the pathogenesis of inflammation.

Results: : The expression of the genes encoding chemokines/cytokines dramatically changed from the start of immunization. Hierarchical cluster analysis from the selected quantitative reverse transcriptase-polymerase chain reaction results showed that gene expression during development and remission of EAU was classified into seven clustering patterns and also discriminated four distinct changes during daily expression (entrance, accelerated, decelerated, and remission phases). Gene expression patterns had good correlation with clinical course of EAU. Gene expressional changes in active phase of EAU displayed the synergetic up-regulation of Th1-type genes (IFN-gamma and CXCL10/IP-10) with elevated Th2-type genes (CCL17/TARC and IL-5). Expression pattern of IFN-gamma corresponding signaling molecule, STAT1, displayed the representative movement of many genes.

Conclusions: : Dynamic expression changes of cytokine and chemokine genes could be involved in the pathogenesis of EAU. Our results suggest that simultaneous upregulation of Th1 and Th2-type inflammatory genes and STAT genes involvement in the development and the remission of EAU.

Keywords: uveitis-clinical/animal model • cytokines/chemokines • gene/expression 
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