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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-10-27
pubmed:abstractText
Tumor necrosis factor-alpha (TNF-alpha) mediates a range of cellular responses, which have potentially detrimental consequences that affect multiple cell types. To determine whether TNF-alpha contributes to glaucomatous optic neuropathy, we have studied the expression of this cytokine and its receptor, tumor necrosis factor receptor-1 (TNF- R1), in human glaucomatous optic nerve heads from patients with different stages of disease using double labeling fluorescence immunohistochemistry. We have also investigated the ability of this cytokine to induce nitric oxide synthase (NOS-2) in cultured human optic nerve astrocytes by immunocytochemistry and immunoblot. Normal tissue showed constitutive expression of TNF-R1 in the vasculature of the optic nerve heads but no positive labeling for TNF-alpha. In the glaucomatous optic nerve heads, the expression of both TNF-alpha and TNF-R1 were apparently upregulated, primarily in glial fibrillary acidic protein (GFAP)-positive astrocytes, and appeared to parallel the progression of optic nerve degeneration. In eyes with severe glaucomatous damage, some HLA-DR positive microglia also contained TNF-alpha and TNF-R1. In the most severely damaged optic nerve heads, the axons of the retinal ganglion cells contained TNF-R1 and, therefore, are direct targets for neurodegeneration caused by TNF-alpha. In vitro astrocytes constitutively express TNF-R1 and TNF-alpha stimulation induces expression of NOS-2. We hypothesize that TNF-alpha contributes to the progression of optic nerve degeneration in glaucoma by both a direct effect on the axons of the retinal ganglion cells and by inducing NOS-2 in astrocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0894-1491
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42-50
pubmed:dateRevised
2011-10-27
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Tumor necrosis factor-alpha: a potentially neurodestructive cytokine produced by glia in the human glaucomatous optic nerve head.
pubmed:affiliation
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't