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Sarah D Ahadome, Chi Zhang, Elizabeth Tannous, Jie J Zheng; Small molecule inhibition of Wnt signaling abrogates dexamethasone induced phenotype of primary trabecular meshwork cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4700.
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© ARVO (1962-2015); The Authors (2016-present)
Steroid induced glaucoma is increased ocular hypertension in glaucoma patients that results from the use of steroids including Dexamethasone (Dex). Dex has been shown to alter trabecular meshwork cell functionality, which can lead to irregular trabecular meshwork structure and therefore decreased outward flow of intraocular fluid. Another important determinant of trabecular meshwork cell mediated extracellular matrix (ECM) regulation is Wnt, the aberrant signaling of which also raises outflow resistance. In our lab we have novel WNT small molecule regulators and thus we wanted to investigate whether these modulators would effect Dex induced phenotype of primary human trabecular meshwork cells.
Primary human TM (hTM) cells treated with Dex (100nM), ethanol vehicle (EtOH, 0.004%) or Dex (100nM) in the presence of WNT inhibitors in vitro, were examined for their collagen production, matrix contraction, α-SMA expression and proliferation. These assays were performed separately at least 2 times and there were greater than 3 technical repeats within each experiment.
Dex treated hTM cells exhibited increased collagen production (p<0.05) and decreased levels of matrix contraction (p<0.05) and α-SMA expression compared to EtOH treated hTM cells. Application of WNT inhibitors together with Dex abolished the effect of Dex on hTM cells whereas WNT activators maintained the Dex phenotype.
Dex induced phenotypic changes in hTM cells in vitro that were consistent with those reportedly contributing to the progression of glaucoma in vivo. Inhibiting the activity of WNT alleviated these Dex mediated effects, which is suggestive that Dex induces glaucomatous hTM cell behavior in a WNT dependent manner. Furthermore this may serve as a model to investigate WNT inhibition as a novel therapeutic strategy for steroid induced glaucoma.
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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