Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 60, Issue 1, Pages 192-201Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.18-25721
Keywords
chemokine; complement; interferon; LCMV; retina; RPE
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Funding
- Lundbeckfonden
- Aase og Ejnar Danielsens Fond
- Danish Eye Research Foundation
- Fight for Sight Denmark
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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.
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