Early pro-inflammatory cytokine elevations in the DBA/2J mouse model of glaucoma

• DOI: 10.1186/s12974-015-0399-0
• Publication Date: 2015-09-17T00:45:52Z
• Authors: Gina N. Wilson; Denise M. Inman; Christine M. Deng...; Matthew A. Smith; Samuel D. Crish
• Keywords: Superior colliculus

Neuroinflammation—astrogliosis, microglial activation, and changes in cytokine signaling—is a prominent feature of neurodegenerative disorders. Glaucoma is group chronic conditions that make up the leading cause irreversible blindness worldwide. Neuroinflammation has been postulated to play significant role pathogenesis progression glaucomatous neurodegeneration. Though much known regarding inflammation eye glaucoma, little about activity outside retina where pathologies develop early. We traced primary visual projection from superior colliculus (SC) DBA/2J DBA/2J.Gpnmb + (control) mice using anterograde tracer cholera toxin-B (CTB) assay axonal transport deficits. Forty-eight hours later, structures were microdissected fresh tissue based on outcome. Using magnetic bead multiplexing assays, we measured levels 20 cytokines retina, proximal distal optic nerves, CTB-positive negative SC subdivisions, cerebellum, serum at different ages representing stages pathology. Pro- anti-inflammatory often changed same direction strain, age, tissue. Significant elevations retinal pro-inflammatory observed young compared controls, followed by an age-dependent decrease mice. Proximal nerve showed 50 % or greater certain older cohorts while both DBA/2Js IL-1β all controls. Pro-inflammatory IL-6 varied accordance with outcome SC: was elevated 44–80 collicular regions deficient ganglion cells (RGCs) areas intact transport. Dysregulation signaling RGC evident early targets, well before intraocular pressure elevation degeneration begins.