Chemokine Expression In Murine Rpe/Choroid In Response To Systemic Viral Infection And Elevated Levels Of Circulating Interferon-Gamma

PURPOSE. To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface.METHODS. Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-gamma. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level.RESULTS. Both the systemic immune activation from virus infection and the sterile systemically increased level of IFN-gamma resulted in increased expression of chemokine ligands, chemokine receptors, and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon alpha/beta receptor or IFN-gamma.CONCLUSIONS. Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokinedependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, AMD, and diabetes.