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Dongli Yang, Bota Cui, Susan Elner, Victor Elner; Upregulation of P2X7 receptor expression by aging, lipopolysaccharide and interferon-γ in the retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1170.
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P2X7 receptors are ligand gated ion channels that respond to extracellular adenosine triphosphate (ATP) and other nucleotide derivatives. P2X7 receptors are involved in oxidative stress, cell death and inflammatory processes, which have been linked to age-related macular degeneration (AMD), the leading cause of irreversible blindness among the elderly. We previously reported that human retinal pigment epithelial (RPE) cells express functional P2X7 receptors and that activation of P2X7 receptors induces RPE apoptosis that underlies AMD. The main purpose of this study was to evaluate whether aging, lipopolysaccharide (LPS) and interferon-γ (IFN-γ) regulate the expression of P2X7 receptors in the RPE.
Eyes from young and old mice, as well as young (early-passage) and senescent (late-passage) human RPE cell cultures derived from donor eyes, were used as experimental models. Real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, immunofluorescence microscopy were performed to evaluate the P2X7 receptor expression at both mRNA and protein levels.
P2X7 receptor protein expression was detected in both young and old mouse retinas, with higher expression level in old RPE cells, compared to cells from young mice. P2X7 receptor protein expression was increased in senescent human RPE cells, compared to young human RPE. Treatment with LPS plus IFN-γ enhanced both P2X7 receptor transcript and protein expression.
This is the first evidence that aging, LPS and IFN-γ increase P2X7 receptor expression in the RPE. These results indicate that upregulation of P2X7 receptor expression by aging and pro-inflammatory factors may contribute to the pathogenesis of AMD.
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