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L. Holmgren, R. M. Sappington; Expression of Interleukin-6 and its Receptor as a Function of Age and Pressure in the DBA/2 Mouse. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4047.
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Microglial interleukin-6 (IL-6) has been shown <i>in vitro<i> to inhibit pressure-induced apoptosis of retinal ganglion cells (RGCs). Here we examined the level and pattern of expression for IL-6 and its receptor (IL-6R) as a function of age and intraocular pressure (IOP) in the DBA/2 mouse model of glaucoma.
Expression and localization of IL-6 and IL-6R was assessed in DBA/2 mice characterized as young (3-4month), median (5-6month) and aged (8-10month) with varying IOP (10mmHg - 28.5mmHg). Expression was measured by semi-quantitative analysis of western blots, while cell-type specific expression was determined by confocal analysis of co-immunolabeling with RGC- and microglia-specific markers.
Whole retina expression of naïve IL-6 increased by as much as 72% with age (p ≤ 0.05), while glycosylated IL-6 decreased by as much as 49% (p ≤ 0.05). With elevated IOP, expression of glycosylated IL-6 increased by 27% in young mice (p ≤ 0.05), but was unaltered in median and aged mice (p ≥ 0.05). In contrast, naïve IL-6 decreased by 44% in aged mice only (p ≤ 0.05). Co-immunolabeling revealed that elevated IOP increased IL-6 expression in microglia of the nerve fiber layer. However, astrocyte expression was also noted in aged mice. IL-6R expression in whole retina was up to 10-fold less in median mice, than in young or aged mice (p ≤ 0.05). IL-6R expression did not change significantly with elevated IOP in young and median mice (p ≥ 0.05), but increased by 52% in aged mice (p ≤ 0.05). Interestingly, immunolabeling revealed that RGC-specific expression of IL-6R actually decreases with both age and elevated IOP.
Our data suggest that elevated IOP in the DBA/2 mouse increases expression of IL-6 in microglia, while decreasing expression of IL-6R in RGCs. However, age altered the basal level of expression as well as the magnitude of pressure-induced changes for both proteins. Interestingly, glycosylation state appears to play a significant role in both age- and pressure-related changes for IL-6.
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