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Fatemeh Suri, Elahe Elahi, Shahin Yazdani, Hamid Ahmadieh, Mozhgan Rezaeikanavi; Oxidative stress effects in glaucoma may be mediated by the TGF-β signaling pathway. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6015.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a progressive optic neuropathy frequently associated with elevated intraocular pressure (IOP) and extracellular matrix (ECM) remodeling at the optic nerve head and in the trabecular meshwork (TM). The pathogenesis is multifactorial and complex, but many recent studies have suggested that transforming growth factor-β (TGF-β) plays a major role in the process. Patients with glaucoma have elevated levels of TGF-β2 in their aqueous humor, and TGF-β has been shown to increase TM ECM production. The bone morphogenetic proteins (BMP) are other members of the TGF-β superfamily of growth factors that modify TGF-β signaling in several different tissues including the TM. For instance, BMP-4 and BMP-7 prevent ECM deposition and strongly antagonize the fibrogenic actions of TGF-β2 on human TM cells. On the other hand, oxidative stress is associated with a large spectrum of neurodegenerative disorders including glaucoma. Many studies have confirmed oxidative stress biomarkers in glaucomatous tissues. In this study, we investigated the role of oxidative stress in TGF-β signaling pathway activation and its effects on ECM genes expression in TM cells.
Cultured human TM cells were exposed to oxidative stress. Oxidative stress was generated in cultured TM cells by exposure to H2O2, and its effects on expression of proteins downstream the TGF-β and BMP signaling pathways was evaluated by Western blot analysis. Additionally, effects on the expression of several ECM related genes were assessed by real time PCR.
Oxidative stress significantly increased activation of the TGF-β signaling pathway, concomitant with decreased activation of the BMP pathway. Oxidative stress also increased expression of some ECM genes in the TM cells.
Oxidative stress in cultured TM cells affects TGF-β and BMP signaling pathways, as well as expression of some ECM related genes. Oxidative stress may exert the same effects on the TM of glaucoma patients, and these may in turn contribute to decreased aqueous humor outflow.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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