Neuroscience

In presence NeuroSeminar: 

The IL-6-STAT3 Axis and Axon Resilience in retinal ganglion cells

Rebecca M. Sappington, PhD

Associate Professor, Dept. Biochemistry

Co-Director, Translational Eye and Vision Research Center

Director, Ocular Biorepository Core Resource

Chair, Faculty Development Council

Wake Forest University School of Medicine

 Venue: to be rescheduled

Host: Marco Feligioni

m.feligioni@ebri.it

Abstract

The association between neuroinflammation and glaucoma progression is long-standing. Studies in human patients and animal models illustrate that complex and dynamic cascades of cytokine signaling are linked to various disease stages and pathological manifestations. In glaucoma and optic nerve injury models, the cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration. As a pleiotropic cytokine, IL-6 possesses both inflammatory and trophic properties, which are highly dependent upon the cellular milieu and molecular context of signaling. Downstream effectors of IL-6 signaling, including STAT3 and mTor, are implicated in a variety of cell survival, death, and recovery pathways in RGCs. However, IL-6 is constitutively expressed in retina, suggesting that IL-6 also performs trophic activities that are not initiated by pathological events. Our recent data indicates that the trophic activities of IL-6 influence the structure and function of RGC axons via a STAT3-mediated pathway that is transcription-independent. In this trophic mechanism, STAT3 interacts with microtubule associated proteins (MAPs) to influence microtubule stability and axon transport facility. STAT3 activity in RGC axons also influences post-translational modification (PTM) of tubulin subunits. Here we present data outlining the role of trophic IL-6 signaling in RGCs and potential implications for RGC susceptibility in optic neuropathy.