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Qian Shi, Qiu Wang, Yu Chen, Xiaodong Sun; A2E induced inflammatory RPE cells impede immune balance of T cell subsets via COX-PGE2 pathways. Invest. Ophthalmol. Vis. Sci. 2014;55(13):70.
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The accumulation of lipofuscin especially A2E with aging in RPE is associated with age related macular degeneration, a disease recently recognized as correlation with immune processes. While accumulating evidences confirm the immunoregulatory function of normal RPE. We hypothesize that A2E could impede immune balance of RPE to inflammatory phenotypes which is implicated in the pathogenesis of AMD.
RPE cells were isolated from B6 mouse and cocultured with CD4+CD25-CD62L+ naive T cells under CD3/CD28 stimulation. These cells were also stimulated with A2E and cocultured with naive T cells in different T subsets polarization conditions. Intracellular cytokines or transcript factors of induced T cells were detected with Flow cytometer. The mechanism underlining A2E influenced RPE immune function were assessed with inhibitors of several pathways .
A2E could stimulate RPE cells to produce inflammatory cytokines and convert naive T cells to inflammatory subsets which express low level of IL-10 and high level of IFN-g. A2E stimulated RPE cells also promote the polarization of Th1 subset in vitro, on the contrary, normal RPE cells impede Th1 differentiation. The mechanism of the A2E induced RPE inflammation involved the pathways of COX2-PGE2 and iNOS-NO.
A2E could convert RPE cells to inflammatory phenotypes which influence the balance of T cells subsets differentiation. This provide evidence link A2E, RPE cells and the immune pathogenesis of AMD.
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