Linked Life Data

16442524

Source:http://linkedlifedata.com/resource/pubmed/id/16442524

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-8
pubmed:abstractText
Mutations in the OPTN gene encoding for optineurin have been associated with primary open-angle glaucoma. The functional role(s) of optineurin in the normal and glaucomatous eye are unclear. As optineurin interferes with TNF-alpha mediated cell death in vitro, an involvement of optineurin in the regulatory pathways leading to apoptosis of retinal ganglion cells has been suggested. The goal of the present study was to study the molecular properties of optineurin and its capabilities to prevent apoptosis in vivo in the eyes of transgenic mice. The chicken betaB1-crystallin promoter was used to overexpress ectopic optineurin in the lenses of transgenic mice. The expression of transgenic mRNA was monitored by northern blot analysis. The localization of transgenic optineurin was investigated by one- and two-dimensional western blot analysis and by immunohistochemistry, and compared with that of endogenous optineurin. To assess effects of transgenic optineurin on apoptosis, betaB1-crystallin-OPTN mice were crossbred with betaB1-crystallin-TGFbeta1 mice that undergo substantial TGF-beta1-induced apoptotic cell death in the lens. Two independent betaB1-crystallin-OPTN transgenic lines were established, in which transgenic optineurin was expressed strictly lens-specific as assessed by Northern and Western blotting, and by immunohistochemistry. In contrast, endogenous optineurin was preferentially expressed in the retina, where retinal ganglion cells showed strong labeling. Immunostaining for endogenous optineurin in the anterior eye was considerably weaker than in the posterior eye and was seen in iris, ciliary epithelium, cells of corneal stroma and endothelium, and in the trabecular meshwork. Neither transgenic nor endogenous optineurin was found in the aqueous humor. Transgenic overexpression of optineurin did not have measurable effects on TGFbeta1-induced apoptosis in mixed betaB1-crystallin-OPTN/betaB1-crystallin-TGFbeta1 transgenic mice. Our results show that optineurin is a cytoplasmatic rather than a secretory protein that is preferentially expressed in retinal ganglion cells, and argue against a major role of optineurin for the modulation of apoptosis in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0014-4835
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1075-85
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16442524-Animals, pubmed-meshheading:16442524-Apoptosis, pubmed-meshheading:16442524-Aqueous Humor, pubmed-meshheading:16442524-Corneal Stroma, pubmed-meshheading:16442524-Endothelium, Corneal, pubmed-meshheading:16442524-Epithelium, Corneal, pubmed-meshheading:16442524-Eye Proteins, pubmed-meshheading:16442524-Gene Expression Regulation, pubmed-meshheading:16442524-Genes, Transgenic, Suicide, pubmed-meshheading:16442524-Immunoblotting, pubmed-meshheading:16442524-Immunohistochemistry, pubmed-meshheading:16442524-In Situ Nick-End Labeling, pubmed-meshheading:16442524-Iris, pubmed-meshheading:16442524-Lens, Crystalline, pubmed-meshheading:16442524-Mice, pubmed-meshheading:16442524-Mice, Transgenic, pubmed-meshheading:16442524-RNA, Messenger, pubmed-meshheading:16442524-Retinal Ganglion Cells, pubmed-meshheading:16442524-Transforming Growth Factor beta, pubmed-meshheading:16442524-Transforming Growth Factor beta1, pubmed-meshheading:16442524-beta-Crystallin B Chain
pubmed:year
2006
pubmed:articleTitle
Transgenic studies on the role of optineurin in the mouse eye.
pubmed:affiliation
Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural