Expression of optineurin, a glaucoma-linked gene, is influenced by elevated intraocular pressure

被引:44
作者
Vittitow, JL [1 ]
Borrás, T [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA
关键词
optineurin; gene expression; human trabecular meshwork; primary open-angle glaucoma; elevated intraocular pressure; perfused; anterior segments; relative quantitative RT-PCR; FIP-2; TNF alpha; dexamethasone;
D O I
10.1016/S0006-291X(02)02395-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Optineurin (optic neuropathy inducing protein; OPTN) was recently linked to 16.7% of families with primary open-angle glaucoma. The function of OPTN in the eye is not known, but is present in the trabecular meshwork, which is responsible for maintenance of intraocular pressure (IOP). To gain insight into the role of OPTN in the development of glaucoma we studied its expression in response to factors known to be associated with the disease: elevated IOP, tumor necrosis factor-alpha (TNFalpha), and dexamethasone (DEX). We performed the treatments in human organ cultures under conditions mimicking physiological pressure. We find OPTN significantly upregulated after 2, 4, and 7 days of sustained elevated IOP. OPTN expression is also induced 2.3-fold by TNFa and 2.6-fold by prolonged DEX treatment. These results demonstrate that OPTN is part of the transcriptome responding to glaucomatous insults and support the protective role of this protein in the trabecular meshwork. (C) 2002 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:67 / 74
页数:8
相关论文
共 31 条
[1]  
Alexander JP, 2001, INVEST OPHTH VIS SCI, V42, P2831
[2]   Adenoviral reporter gene transfer to the human trabecular meshwork does not alter aqueous humor outflow.: Relevance for potential gene therapy of glaucoma [J].
Borrás, T ;
Rowlette, LL ;
Erzurum, SC ;
Epstein, DL .
GENE THERAPY, 1999, 6 (04) :515-524
[3]  
Borrás T, 2002, INVEST OPHTH VIS SCI, V43, P33
[4]  
Bradley JMB, 2000, INVEST OPHTH VIS SCI, V41, P422
[5]   Inefficient processing of an olfactomedin-deficient myocilin mutant:: Potential physiological relevance to glaucoma [J].
Caballero, M ;
Borrás, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 282 (03) :662-670
[6]   Altered secretion of a TIGR/MYOC mutant lacking the olfactomedin domain [J].
Caballero, M ;
Rowlette, LLS ;
Borrás, T .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2000, 1502 (03) :447-460
[7]  
Cotinet A, 1997, GLIA, V20, P59, DOI 10.1002/(SICI)1098-1136(199705)20:1<59::AID-GLIA6>3.3.CO
[8]  
2-6
[9]   FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates cellular morphogenesis [J].
Hattula, K ;
Peränen, J .
CURRENT BIOLOGY, 2000, 10 (24) :1603-1606
[10]   Ultrastructural changes in the trabecular meshwork of human eyes treated with corticosteroids [J].
Johnson, D ;
Gottanka, J ;
Flugel, C ;
Hoffmann, F ;
Futa, R ;
LutjenDrecoll, E .
ARCHIVES OF OPHTHALMOLOGY, 1997, 115 (03) :375-383