Induced Autoimmunity to Heat Shock Proteins Elicits Glaucomatous Loss of Retinal Ganglion Cell Neurons via Activated T-Cell-Derived Fas-Ligand

摘要: Glaucomatous optic neuropathy causes blindness through the degeneration of retinal ganglion cells (RGCs) and their axons, which comprise nerve. Glaucoma traditionally is associated with elevated intraocular pressure, but often occurs or may progress pressure in normal range. Like other diseases CNS, a subset glaucoma has been proposed to involve an autoimmune component help explain loss RGCs absence pressure. One hypothesis involves heat shock proteins (HSPs), because increased serum levels HSP autoantibodies are prominent some patients pressures. In first direct support this hypothesis, we found that HSP27 HSP60 immunization Lewis rat induced RGC axon 1-4 months later vivo pattern similarities human glaucoma, including topographic specificity cell loss. Infiltration numbers T-cells retina occurred much earlier, 14-21 d after immunization, appeared be transient. vitro studies activated by apoptosis via release inflammatory cytokine FasL, whereas activation microglia upregulation FasL receptor RGCs. summary, our results suggest for selected individuals likely failed immunoregulation T-cell-RGC axis thus disturbance both proapoptotic protective pathways.