Role of Interleukin-6 in Health and Disease of Retinal Ganglion Cells

Abstract

Neuroinflammation is defined as inflammation that occurs in the central nervous system (CNS) and is characterized by cytokine release and glial reactivity. Previous efforts indicate that neuroinflammation is involved in many facets of the CNS, including development, homeostatic maintenance, and degeneration in response to injury and disease. Elucidating how specific cytokines are involved in these facets is important for the development of new therapies as well as expanding our knowledge of how the CNS develops, functions, and responds to stress. Using the optic projection as a model of the CNS, this thesis investigates how the cytokine interleukin-6 (IL-6): 1) contributes to the constitutive development and function of retinal ganglion cells (RGCs) and 2) impacts degeneration of RGCs in response to glaucoma-related stressors (i.e. ocular hypertension). Our data indicate that IL-6 signaling is necessary for proper development and function of RGC axons, yet facilitates axon degeneration and vision loss in response to ocular hypertension. The apparent switch of IL-6 from a constructive signal to a destructive signal correlates with elevations in the soluble isoform of the IL-6 receptor (sIL-6Rα), an isoform that is linked to degeneration within and outside the CNS.