title: Interleukin-6: A Constitutive Modulator of Glycoprotein 130, Neuroinflammatory and Cell Survival Signaling in Retina.
abstract: OBJECTIVE
  The interleukin-6 (IL-6) family of cytokines and their signal transducer glycoprotein (gp130) are implicated in inflammatory and cell survival functions in glaucoma. There are several avenues for interdependent modulation of IL-6 family members and gp130 signaling. Here we investigated whether IL-6 modulates gp130 and related neuroinflammatory, cell survival and regulatory signaling in both healthy and glaucomatous retina.
  
  
  METHODS
  In naïve and glaucomatous (Microbead Occlusion Model), wildtype (WT) and IL-6 knockout (IL-6-/-) mice, we examined gp130 protein expression and localization, using western blot and immunohistochemistry. Gene targets related to IL-6 and gp130 signaling and pertinent to neuroinflammation (TNFα, IL-1β), cell health (Bax, Bcl-xl) and STAT3 regulation (Socs3) were quantified using qRTPCR.
  
  
  RESULTS
  In the naïve retina,IL-6-/-retina contained significantly less gp130 compared to WT retina. This IL-6-related decrease in gp130 was accompanied by a reduction in mRNA expression ofTNFα,Socs3andBax. After 4 weeks of microbead-induced ocular hypertension, both microbead- and saline-injected (control) eyes ofIL-6-/-mice exhibited higher expression ofTNFα, compared to WT mice.IL-1βexpression was also reduced specifically inIL-6-/-retina with microbead-induced glaucoma. While saline and microbead injection increasedBcl-xlandSocs3mRNA in both WT andIL-6-/-mice,IL-6-/-deficiency led to smaller increases for bothBcl-xlandSocs3.
  
  
  CONCLUSIONS
  Our findings support a role for IL-6 in setting baseline parameters for neuroinflammatory, cell health and gp130 regulatory signaling that can impact the nature and magnitude of retinal responses to glaucoma-related stressors.
authors.affiliation: Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA.
authors.forename: Franklin D
authors.initials: FD
authors.lastname: Echevarria
authors.affiliation: Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Abigayle E
authors.initials: AE
authors.lastname: Rickman
authors.affiliation: Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Sappington
keywords: Glaucoma; Gp130; Inflammation; Interleukin-6; Retina