June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Cleavage of IL-6 receptor alpha as a potential mechanism for IL-6 transsignaling in Glaucoma
Author Affiliations & Notes
  • Payton Russom
    Dept. Biological Sciences, Vanderbilt University, Nashville, TN
    Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, TN
  • Cathryn Formichella
    Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, TN
  • Rebecca Sappington
    Vanderbilt Eye Institute, Vanderbilt University School of Medicine, Nashville, TN
    Dept. Pharmacology, Vanderbilt University School of Medicine, Nashville, TN
  • Footnotes
    Commercial Relationships Payton Russom, None; Cathryn Formichella, None; Rebecca Sappington, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 786. doi:
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      Payton Russom, Cathryn Formichella, Rebecca Sappington; Cleavage of IL-6 receptor alpha as a potential mechanism for IL-6 transsignaling in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):786.

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

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Abstract

Purpose: Previous work suggests that interleukin-6 (IL-6) signaling via both classical and transsignaling pathways may be important for retinal ganglion cell survival (RGC) in glaucoma. Here we evaluate the possibility that IL-6 transsignaling is mediated by cleavage of membrane-bound IL-6 receptor alpha (IL-6Rα) by metalloproteinases ADAM10 and ADAM17.

Methods: Using immunolabeling and immunoblotting, we examined the expression and localization patterns of ADAM10 and ADAM17 in whole eye paraffin sections and protein lysates from glaucomatous DBA/2 and control C57 mice. We then perfomred co-localization studies to compare expression and localization patterns of ADAM10 and ADAM17 and their potential target, IL-6Rα. Cell type-specific markers were used to confirm retinal ganglion cell (β-tubulin), rod bipolar cell (PKCα) and Muller glial cell (glutamine synthetase) identities.

Results: We found that both ADAM10 & ADAM17 are expressed in healthy and glaucomatous retina, where they localize to multiple layers. Co-immunolabeling revealed that ADAM10 and ADAM17 are primarily expressed by RGCs, which also express IL-6Rα. Quantification of ADAM10 and ADAM17 expression in the ganglion cell and nerve fiber layers of retina revealed that while ADAM10 expression did not change significantly with age (p > 0.05) or IOP (p > 0.05), elevated IOP increased ADAM17 expression by up to 55% (p = 0.03). There was no age-related increase in ADAM17 expression (p > 0.05).

Conclusions: Our data suggests that the necessary machinery (ADAM 10 & ADAM 17) is present in RGCs to cleave existing membrane-bound IL-6Rα into soluble IL-6R. Interestingly, elevated IOP only altered the expression ADAM17 by RGCs. This suggests that ADAM17, in particular, may be a mechanism for the induction of IL-6 transsignaling in glaucoma.

Keywords: 490 cytokines/chemokines • 531 ganglion cells  
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