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J. Tombran-Tink, K. Leung, J. M. Burke, C. J. Barnstable; A Role for the Retinal Pigmented Epithelium in Ocular Inflammation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4761.
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Inflammation underlies the progression of many retinal degenerative diseases. Here we examined the role of the RPE in inflammatory processes in the retina.
The transcriptome for the human RPE cell line, ARPE19 was examined using a 28K human array. Expression of a large group of inflammatory mediators was identified and confirmed by PCR and immunocytochemistry in primary cultures of human RPE cells of various ages and ARPE19. Age-related changes in cytokine secretion in primary cultures and modulations in cytokine expression by ARPE19 after treatment with lipopolysaccharide (LPS) were measured using the Luminex bead immunoassay. The effects of LPS on ARPE19 survival, cytokine secretion, and cytokine receptor expression were also examined. The actions of two pro-inflammatory cytokines, IL-6 and IL-8, on RPE survival were determined using MTT assay and by gene silencing of IL-6R and IL-8R using the receptors’ target siRNA.
Primary cultures of human RPE cells and ARPE19 express 19/25 cytokine receptors examined, with a decrease or lack of expression of many of these with increased aging of the RPE. Increases in the proinflammatory cytokines, MCP-1, IL-6, IL-8, and VEGF correlate with increased RPE age. The anti-inflammatory mediators IL-4 and IL-13 are secreted at higher concentrations by younger RPE cells. LPS increases production of IL-4, -6, -8. -10, IFN, and MCP-1, promotes transcription of IL-13RA1 and IFNAR1, and decreases IL-7R mRNA in ARPE19. LPS induces RPE cell death at concentrations above 10 ug/ml. LPS induced cell death is mediated through IL-6 and IL-8 and can be blocked by gene silencing of the IL-6 and IL-8 receptors.
We propose that the RPE plays a pivotal role in retinal degenerations associated with acute inflammation because of its expression of a wide array of immune receptor targets, its increased expression of proinflammatory cytokines including VEGF with increased aging, its acute response to bacterial toxin, and because of its ready access in the retina to plasma levels of inflammatory mediators
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