Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ

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-transcrip...

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Bibliographic Details
Published in:Investigative ophthalmology & visual science 2019-01, Vol.60 (1), p.192-201
Main Authors: Faber, Carsten, Juel, Helene Bæk, Jensen, Benjamin Anderschou Holbech, Christensen, Jan Pravsgaard, Prause, Jan Ulrik, Thomsen, Allan Randrup, Nissen, Mogens Holst
Format: Article
Language:English
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Summary: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.
ISSN:1552-5783
1552-5783
DOI:10.1167/iovs.18-25721