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Rudolf Fuchshofer, Magdalena Schneider; Decorin, a modulator of TGF-β2 and CTGF signaling in the trabecular meshwork. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3292.
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The critical risk factor for optic nerve damage in primary open-angle glaucoma (POAG), is an increased intraocular pressure (IOP) caused by an increased outflow resistance in the trabecular meshwork (TM). The molecular pathogenesis of the increased outflow resistance has not been identified, but TGF-β2 and CTGF may be involved. Both growth factors contribute to an increased ECM synthesis and to an increased contraction rate in the TM and thereby can lead to an increased outflow resistance. In a healthy eye the growth factors are in a homeostatic balance, which seems to be disturbed in POAG. In this study we investigated the influence of Decorin (DCN), a potential endogenous antagonist of TGF-β2 and CTGF, on the expression of growth factors, ECM and actin cytoskeleton components in vitro and in vivo.
For that purpose we analyzed the DCN knockout mice in comparison to the wild-type littermates with different ages. Further we investigated the effects of DCN in vivo and in vitro on TM by real-time RT-PCR, immunoblotting, immunohistochemistry and light microscopy. IOP was measured by tonometry. The total number of myelinated optic nerve axons were counted in DCN knockout mice and wild-type littermates with different ages.
The DCN treatment led to a decreased synthesis of CTGF, TGF-β1 and 2 in HTM cells, accompanied by a reduced expression of ECM proteins. We show that the deficiency of DCN increases IOP and leads to optic nerve damage in mouse eyes. These changes were associated with an induction of CTGF, fibronectin and α-smooth muscle actin in the TM of the DCN deficient animals.
Our results strongly indicate that DCN is a modulator of TGF- β2 and CTGF signaling in the trabecular meshwork, contributing to the homeostatic balance of growth factors. DCN could be a promising modifier of TGF-β2 and CTGF signaling in POAG.
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