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Abstract #26956 Published in IGR 12-4
TGF-{beta}2 induces senescence-associated changes in human trabecular meshwork cells.
Yu AL; Birke K; Moriniere J; Welge-Lüssen UInvestigative Ophthalmology and Visual Science 2010; 51: 5718-5723
See also comment(s) by Tina Wong •
PURPOSE: Recent studies have revealed an accumulation of senescent cells in the outflow pathways in primary open-angle glaucoma (POAG). Transforming growth factor (TGF)-β2 is thought to be involved in the pathologic changes of the trabecular meshwork (TM) of POAG eyes. The goal of this study was to determine whether TGF-β2 triggers senescence-associated changes in human TM cells in vitro. METHODS: Cultured human TM cells were exposed to 1.0 ng/mL TGF-β2 for 12, 24, and 48 hours. Senescence-associated β-galactosidase (SA-β-Gal) activity was investigated by histochemical staining. Lipid peroxidation was assessed after TGF-β2 treatment. Levels of apolipoprotein J (Apo J), SM22, and osteonectin (SPARC) mRNA were determined by real-time PCR analysis. Furthermore, the effects of antioxidants on these TGF-β2-mediated changes were tested. Induction of senescence-related signal transduction proteins (p16, p21, and pRb) was examined by real-time PCR and Western blot analysis. RESULTS: TGF-β2 increased SA-β-Gal activity, lipid peroxidation, and the mRNA expressions of Apo J, SM22, and SPARC. These TGF-β2-induced changes were attenuated by antioxidants. TGF-β2 increased p16 mRNA and protein expression, which was paralleled by a downregulation of pRb protein. There was no effect on p21 mRNA and protein expression after exposure to TGF-β2. CONCLUSIONS: TGF-β2 induces senescence-associated TM changes and activates the senescence-related p16-pRb signal transduction pathway in vitro. Thus, minimizing TGF-β2 levels may help to prevent the ageing process in the TM as seen in POAG.
Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany.
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)