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Abstract #15663 Published in IGR 2-3
Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured petinal ganglion cells
Tezel G; Wax MBJournal of Neuroscience 2000; 20: 8693-8700
Although glial cells in the optic nerve head undergo a reactivation process in glaucoma, the role of glial cells during glaucomatous neurodegeneration of retinal ganglion cells is unknown. Using a coculture system in which retinal ganglion cells and glial cells are grown on different layers but share the same culture medium, the authors studied the influences of glial cells on survival of retinal ganglion cells after exposure to different stress conditions typified by simulated ischemia and elevated hydrostatic pressure. After the exposure to these stressors, the authors observed that glial cells secreted tumor necrosis factor-α (TNF-α), as well as other noxious agents such as nitric oxide, into the coculture media and facilitated the apoptotic death of retinal ganglion cells as assessed by morphology, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling, and caspase activity. The glial origin of these noxious effects was confirmed by passive transfer experiments. Furthermore, retinal ganglion cell apoptosis was attenuated approximately 66% by a neutralizing antibody against TNF-α and 50% by a selective inhibitor of inducible nitric oxide synthase (1400 W). Because elevated intraocular pressure and ischemia are two prominent stress factors identified in the eyes of patients with glaucoma, these findings reveal a novel glia-initiated pathogenic mechanism for retinal ganglion cell death in glaucoma. In addition, these findings suggest that the inhibition of TNF-α that is released by reactivated glial cells may provide a novel therapeutic target for neuroprotection in the treatment of glaucomatous optic neuropathy.
Dr. G. Tezel, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
11.8 Neuroprotection (Part of: 11 Medical treatment)
