April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Expression of Interleukin-6 and its Receptor as a Function of Age and Pressure in the DBA/2 Mouse
Author Affiliations & Notes
  • L. Holmgren
    Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee
  • R. M. Sappington
    Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee
  • Footnotes
    Commercial Relationships  L. Holmgren, None; R.M. Sappington, None.
  • Footnotes
    Support  Glaucoma Research Foundation: Catalyst for a Cure Consortium (David J. Calkins)
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4047. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: cytokines/chemokines • glia • ganglion cells 
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