Abstract:
PURPOSE:Oxidative stress and cellular senescence are known to contribute to the development of AMD; however, the mechanism is not fully understood. This study investigated the role of TGF-β-activated kinase 1 (TAK1) in the senescence of RPE cells as a model for the development of dry AMD. METHODS:Cultured human RPE cells were treated with the TAK1 inhibitor 5Z-7-oxozeaenol for 1 hour, and then treated with 200 μM hydrogen peroxide for 1 hour. Human RPE cells that were not pretreated with TAK1 inhibitor for 1 hour served as controls. Senescence-associated β-galactosidase (SA-β-gal) activity was detected by histochemistry, and p53 expression by immunoblotting. Cell-cycle and apoptosis rate in RPE cells were determined by flow cytometry. RESULTS:The TAK1 expression in human RPE cells was high and was altered on oxidative stress. Transforming growth factor-β-activated kinase 1 inhibition led to reduction in cell proliferation, cell-cycle arrest at G0/G1, and increased SA-β-gal expression, all known to be features of cell senescence. Exposure of cells to oxidative stress combined with inhibition of TAK1 activity decreased the expression of apoptotic proteins, such as p53, and promoted cellular senescence. Aberrant TAK1 activity in RPE cells triggered their secretion of factors that induced hypertrophy and fibrotic changes in neighboring cells. CONCLUSIONS:The in vitro evidence indicated a role for TAK1 in the onset of senescence in RPE cells. The data shown hereby demonstrated that TAK1 activity is essential for maintaining normal function of RPE cells. Elucidation of its role in mechanisms underlying RPE cellular senescence induction may potentiate development of powerful tools for halting the development of dry AMD.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Dvashi Z,Green Y,Pollack Adoi
10.1167/iovs.14-14349subject
Has Abstractpub_date
2014-08-12 00:00:00pages
5679-86issue
9eissn
0146-0404issn
1552-5783pii
iovs.14-14349journal_volume
55pub_type
杂志文章abstract:PURPOSE:Human adenovirus species D type 19 (HAdV-D19) has been associated with epidemic keratoconjunctivitis (EKC), a highly inflammatory infection of the ocular surface. Confusion exists regarding the origins of HAdV-D19. The prototype virus (HAdV-D19p) does not cause EKC, while a virus identified later with the ident...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-9656
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abstract:Purpose:To evaluate spontaneous and evoked ocular sensory responses in rats after denervation of the lacrimal gland, as well as protein changes in tears that may mediate functional changes. Methods:Sprague-Dawley rats served as subjects. The left lacrimal gland was partially denervated with saporin toxin conjugated to...
journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.18-25267
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abstract:PURPOSE:To determine whether a novel peroxynitrite-based photosensitizer S-nitrosoglutathione (GSNO) can produce specific in vitro light-induced cell death of both standard animal lung and human Tenon's capsule (TC) fibroblasts and to compare this effect with that produced by the established photodynamic porphyrin prec...
journal_title:Investigative ophthalmology & visual science
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doi:
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abstract:PURPOSE:To determine the effect of dilute alcohol on human corneal epithelial cellular morphology and viability. Dilute alcohol is used for epithelial removal during photorefractive keratectomy (PRK) and laser subepithelial keratomileusis (LASEK). METHODS:Corneal epithelial sheets harvested from human eyes after alcoh...
journal_title:Investigative ophthalmology & visual science
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doi:
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abstract:PURPOSE:Equine recurrent uveitis (ERU) is an incurable disease affecting the inner eye that leads to blindness, through activated T cells that pass the blood-retinal barrier and destroy the retina. Serum markers are a desirable choice for monitoring development of disease, as serum is easy accessible and the markers co...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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abstract:PURPOSE:Fractal dimension of retinal vasculature is a global summary measure of retinal vascular network pattern and geometry. This study was conducted to examine the effect of variations in image color, brightness, focus, contrast, and format on the measurement of retinal vascular fractal dimension. METHODS:A set of ...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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更新日期:2018-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1982-09-01 00:00:00
abstract:PURPOSE:To develop an eye-motion-tracking optical coherence tomographic (OCT) method and assess its effect on image registration and nerve fiber layer (NFL) thickness measurement reproducibility. METHODS:A system capable of tracking common fundus features based on reflectance changes was integrated into a commercial O...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2013-09-09 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1990-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2001-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1987-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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更新日期:2004-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1988-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
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更新日期:2003-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Topical application of Prostaglandin F2 alpha (PGF2 alpha) to the eye reduces intraocular pressure (IOP) in all mammalian species studied thus far, including humans. The L-isopropylester derivative is currently the one most commonly used in experimental and clinical studies. Dose-response relationships were determined...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2017-03-01 00:00:00