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Bernadette Marrero, Yu Chen-Rong, Chandrasekharam Nagineni, Charles Egwuagu; Temporal Expression of miR-155 Correlates with the initiation and Development of Experimental Autoimmune Uveitis (EAU). Invest. Ophthalmol. Vis. Sci. 2012;53(14):6238.
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MicroRNAs are small non-coding genes that regulate diverse cellular processes in vertebrates. Aberrant or enhanced expression of several miRNAs including miR-146, miR-21, Let-7e and miR-155 are associated with several pathogenic conditions of humans. For example, miR-155 has recently been implicated in the pathogenesis of CNS inflammatory diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). In this study, we have investigated potential involvement of miR-155 in intraocular inflammatory disease or uveitis.
To investigate the potential involvement of miR-155 in ocular inflammatory diseases, we induced experimental autoimmune uveitis (EAU) in C57BL/6 mice by active immunization with IRBP in CFA. Severity and progression in EAU were assessed by fundoscopy and histopathology. miRNA expression in human retinal cells (ARPE-19), as well as, in the retina of mice with EAU was analyzed by real-time quantitative PCR.
Analysis of inflammatory cells in the retina during EAU revealed a 5.3-fold increase of miR-155 expression in the retina compared to un-immunized mice. The increase in miR-155 expression correlated temporally with increase in pro-inflammatory cytokines and progression of EAU. In addition, culturing human RPE cells in medium containing pro-inflammatory cytokines induced an even a more dramatic increase in miR-155 compared to untreated cells.
Dramatic increase of miR-155 in the retina during ocular inflammation and following exposure of ocular cells to inflammatory environment was dramatic and suggest that miR-155 may be implicated in mechanisms that promote of T cell-dependent tissue inflammation. Our data further suggest that miR-155 might be a promising therapeutic target for the treatment of uveitis and other autoinflammatory disorders.
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