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

Neuroinflammation, defined as the induction of immune-related processes within the central nervous system, 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.