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Abstract #21949 Published in IGR 10-4
TNF-α signaling in glaucomatous neurodegeneration
Tezel GProgress in Brain Research 2008; 173: 409-421
Growing evidence supports the role of tumor necrosis factor-alpha (TNF-α) as a mediator of neurodegeneration in glaucoma. Glial production of TNF-α is increased, and its death receptor is upregulated on retinal ganglion cells (RGCs) and optic nerve axons in glaucomatous eyes. This multifunctional cytokine can induce RGC death through receptor-mediated caspase activation, mitochondrial dysfunction, and oxidative stress. In addition to direct neurotoxicity, potential interplay of TNF-α signaling with other cellular events associated with glaucomatous neurodegeneration may also contribute to spreading neuronal damage by secondary degeneration. Opposing these cell death-promoting signals, binding of TNF receptors can also trigger the activation of survival signals. A critical balance between a variety of intracellular signaling pathways determines the predominant in vivo bioactivity of TNF-α as best exemplified by differential responses of RGCs and glia. This review focuses on the present evidence supporting the involvement of TNF-α signaling in glaucomatous neurodegeneration and possible treatment targets to provide neuroprotection.
Dr. G. Tezel, Departments of Ophthalmology and Visual Sciences and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, USA. Gulgun.tezel@louisville.edu
