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AF Clark, W-H Wang, LG McNatt, P Hellberg, I-H Pang, JS Rubin, JH Fingert, VC Sheffield, EM Stone; Increased Expression of sFRP-1 in Glaucomatous Trabecular Meshwork and Presence of a Functional WNT Signaling Pathway that Regulates IOP . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4095.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify differentially expressed genes in glaucomatous trabecular meshwork (TM) cells and to determine the possible function(s) of these genes in the TM and in glaucoma pathogenesis. Methods: RNA differential display, quantitative RT-PCR, and western blotting were used to identify genes differentially expressed in 7 sets of age-matched normal and glaucomatous human TM cells. RT-PCR and western immunoblotting were used to identify members of the WNT signaling pathway in TM cells. Recombinant FRP-1 was added to perfusion cultured human eyes to determine effects on the aqueous outflow facility. Results: Expression of the WNT antagonist sFRP-1 mRNA and protein was 5 fold higher in glaucomatous TM cells. Genes involved in the WNT signaling pathway, including WNTs 2B & 5A and Frizzled 1, 2, 7 & G736678 were expressed in TM cells. There was an inverse relationship between protein levels of sFRP-1 and the WNT signaling mediator beta-catenin, suggesting that TM cells have a functional WNT signaling system. The addition of recombinant sFRP-1 to perfusion cultured human eyes (n=4-6) caused a decrease in outflow facility (45-62%, p<0.05) as well as a decrease in beta-catenin levels in the TM and ciliary body (41-55%, p<0.05). Conclusion: TM cells have a functional WNT signaling pathway, which may play an important role in normal TM cell function. Increased expression of sFRP-1, which occurs in glaucomatous TM cells, blocks WNT signaling and causes decreased aqueous outflow.
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