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Heather M. Cathcart, Rebecca M. Sappington; Soluble IL-6R and Neuroprotection of Retinal Ganglion Cells in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6585.
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Interleukin-6 (IL-6) trans-signaling mediated through soluble IL-6 receptor (sIL-6R) plays a critical role in the pathology of numerous chronic inflammatory diseases. The objective of this study was to examine the neurobiological relevance of IL-6 trans-signaling in the onset and progression of retinal ganglion cell (RGC) pathology in a chronic murine model of glaucoma.
Using a co-immunolabeling assay, the presence of sIL-6R and transmembrane IL-6R alpha (IL-6R alpha) were assessed simultaneously in whole mount retinas. For this assay, two antibodies against IL-6R were used; the first is specific to the cytoplasmic peptide sequence, while the second is specific to the extracellular sequence. IL-6R alpha was identified by co-localization of both antibodies whereas sIL-6R was revealed by the presence of only the extracellular antibody. Furthermore, IL-6R alpha, sIL-6R, gp130 and soluble gp130 (sgp130) were quantified from whole retina fractions of soluble and trans-membrane protein and both fractions were analyzed using the Milliplex Map mouse soluble cytokine receptor immunoassay.
In retina whole mounts from 4 and 7 month old DBA/2 and C57BL/6 mice, we found that both forms of IL-6R were associated with SMI-31 in RGCs. However, localization of IL-6R alpha was primarily associated with RGC somas in C57BL/6 mice, while strong sIL-6R labeling was associated with RGC axons in DBA/2 mice. The cytokine receptor immunoassay confirmed that membrane bound IL-6R alpha concentration increased in DBA/2 (19.48 pg/ml) retinas when compared to retinas from C57BL/6 (14.74 pg/ml) mice. The immunoassay also revealed that sIL-6R was slightly decreased in DBA/2 (5.08 pg/ml) retinas when compared with concentrations from retinas of C57BL/6 (7.14 pg/ml) mice. Concentrations of the common signal transduction protein, gp130, was also decreased in DBA/2 retinas (137.36 pg/ml; C57BL/6 224.17 pg/ml), while sgp130 concentrations were similar (DBA/2 7.70 pg/ml; C57BL/6 8.61 pg/ml).
These data indicate that sIL-6R is associated with RGC axons and somas and that soluble and transmembrane IL-6R and gp130 expression varies with increased intraocular pressure, implicating IL-6 trans-signaling in RGC pathology in chronic glaucoma.
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