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Carsten Faber, Helene Bæk Juel, Benjamin Anderschou Holbech Jensen, Jan Pravsgaard Christensen, Jan Ulrik Prause, Allan Randrup Thomsen, Mogens Holst Nissen; Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ. Invest. Ophthalmol. Vis. Sci. 2019;60(1):192-201. doi: https://doi.org/10.1167/iovs.18-25721.
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To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface.
Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level.
Both the systemic immune activation from virus infection and the sterile systemically increased level of IFN-γ 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 α/β receptor or IFN-γ.
Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent 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.
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