AJND Copyright © Since 2012-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA
Am J Neurodegener Dis 2012;1(2):168-179

Original Article
Spatial regulation of interleukin-6 signaling in response to
neurodegenerative stressors in the retina

Stephanie M Sims, Lauren Holmgren, Heather M Cathcart, Rebecca M Sappington

Department of Ophthalmology and Visual Sciences, Department of Pharmacology, Vanderbilt University School of
Medicine, Nashville, TN, USA.

Received July 13, 2012; accepted June 31, 2012; Epub August 1, 2012; published August 15, 2012

Abstract: Neuroinflammation, defined as the induction of immune-related processes within the central nervous
system (CNS), is recognized as a component of many neurodegenerative disorders, including glaucomatous
degeneration of retinal ganglion cells (RGCs). Previous work in vitro identified IL-6 as a potential neuroprotective factor
for RGCs, particularly those challenged by glaucoma-related stressors. Here we examined the temporal and spatial
characteristics of IL-6 signaling in response to two stressors related to RGC neurodegeneration: age and elevated
intraocular pressure (IOP). Using ELISA, immunoblotting, immunolabeling and quantitative microscopy, we measured
and compared whole retina and RGC-related expression of IL-6 and IL-6Rα in normal retina (young C57), retina
susceptible to glaucomatous neurodegeneration (young DBA/2), aging retina (aged C57) and aging retina challenged
by elevated IOP (aged DBA/2). We found that: 1) neurodegenerative stressors induce alterations in whole retina
expression of IL-6 and IL-6Rα, 2) these whole retina changes do not reflect the immediate milieu of RGCs, where IL-6
and IL-6Rα expression is spatially variable and 3) the extent and magnitude of this spatial variability is stressor-
dependent. Our data provide the first evidence that neurodegenerative stressors produce microenvironments of IL-6
signaling in retina and that the nature and magnitude of spatial regulation is dependent on the identity of the stressor.

Keywords: Retina, DBA/2, interleukin-6, interleukin-6 receptor, glaucoma

Address all correspondence to:
Rebecca M Sappington, PhD
Department of Ophthalmology and Visual Sciences
The Vanderbilt Eye Institute, Vanderbilt University Medical Center
11445E Medical Research Building  IV, Nashville, TN 37232-0654, USA.
Tel: 615-322-0790; Fax: 615-936-1594
E-mail: rebecca.m.sappington@vanderbilt.edu