Cytokine release from non-inflammatory cells is a key step in innate immunity, and agonists triggering cytokine release are central in coordinating responses. P2X7 receptor (P2X7R) stimulation by extracellular ATP is best known to active the NLRP3 inflammasome and release IL-1β, but stimulation also leads to release of other cytokines. As cytokine signaling by retinal pigmented epithelial (RPE) cells is implicated in retinal neurodegeneration, the role of P2X7R in release of cytokine IL-6 from RPE cells was investigated. P2X7R stimulation triggered IL-6 release from primary mouse RPE, human iPS-RPE and human ARPE-19 cells. IL-6 release was polarized, with predominant rise across apical membranes. IL-6 release was inhibited by P2X7R antagonists A438079, A839977, and AZ10606120, but not the NRTI lamivudine (3TC), P2X1R antagonist NF279, or P2Y1R antagonist MRS2179. P2X7R-mediated IL-6 release required extracellular Ca2+ and was blocked by Ca2+ chelator BAPTA. IL-6 release and Ca2+ elevation occurred rapidly, consistent with vesicular IL-6 staining in unstimulated cells. P2X7R stimulation did not trigger IL-1β release in these unprimed cells. P2X7R-mediated IL-6 release was enhanced in RPE cells from the ABCA4−/− mouse model of retinal degeneration. In summary, P2X7R stimulation triggers rapid Ca2+-dependent IL-6 release across the apical membrane of RPE cells.

Choroid has been proposed to participate in the regulation of light refraction by changing its thickness. The present study aims to analyze the characteristics of choroidal thickness (CT), and its correlation with refractive error, axial length and age in young ametropia. A total of 51 subjects (102 eyes), aged from 5 to 18 years old (mean age 10.04 ±2.78 years), with ametropia were included in the study. Choroidal imaging was obtained by enhanced depth imaging (EDI) of spectral domain Optical Coherence Tomography (OCT). CT was horizontally measured at 5 locations in across fovea with 1mm interval. We found that the spherical equivalent refractive diopter was from -7.25D to 1.6D (mean, -1.61D±1.82D), the mean axial length was 24.14mm±1.14mm. The closer to the optic disc the thinner the choroid is. CT between fovea and disc showed better correlation with refractive error (p< 0,01), axial length (p<0.01) and age (P<0.05) than those temporal to fovea. Our results indicated that the choroid is least thick around the optic disc. Thickness between fovea and optic disc is significantly associated with refractive error, axial length and age in growing adolescences. This result may help us understand the function of choroid during ametropic progression.

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