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Originally published In Press as doi:10.1167/iovs.07-1295 on February 15, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:1957-1970.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1295
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Differentially Expressed Genes in MHC-Compatible Rat Strains That Are Susceptible or Resistant to Experimental Autoimmune Uveitis

Mary J. Mattapallil,1 Andrea Augello,2 Chris Cheadle,3 Diane Teichberg,3 Kevin G. Becker,3 Chi-Chao Chan,1 Joseph J. Mattapallil,4 Giuseppina Pennesi,*,2 and Rachel R. Caspi*,1

1From the Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland; the 2Department of Oncology, Biology, and Genetics, University of Genoa, and National Institute for Cancer Research, Genoa, Italy; the 3DNA Array Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland; and the 4Department of Microbiology and Immunology, F. Edward Hebert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland.

PURPOSE. Experimental autoimmune uveitis (EAU) is an established model for immune-mediated human uveitis. Although several genes from major histocompatibility complex (MHC) loci have been shown to play a role in uveitis, little is known about the role of non-MHC genes in the pathogenesis of EAU. Several non-MHC genes have been implicated in the pathogenesis of various autoimmune diseases. The primary objective of this study was to identify the non-MHC genes involved in the pathogenesis of EAU, to identify potential drug targets and possibly to target their protein products for immunotherapy.

METHODS. EAU was induced in the susceptible (Lewis; LEW) or resistant (Fischer 344; F344) rats that have identical MHC class II haplotype. Draining lymph node cells were obtained during the innate and adaptive phase of the immune response, and the pattern of gene expression was evaluated using microarray technology. Differentially expressed genes were validated at mRNA and protein levels using various methods.

RESULTS. Susceptibility to EAU was associated with an increased expression of numerous non-MHC genes such as Th1-type cytokines and chemokines, antiapoptotic factors, hormones, and neurotransmitters and a downregulation of selected adhesion molecules. In this study a combined genetic-genomic approach was used to identify different patterns of gene expression associated with the sensitization and effector phase of EAU pathogenesis.

CONCLUSIONS. The data demonstrate that the differential expression of several non-MHC genes is associated with the mechanism of uveitis.






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