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Abstract #23725 Published in IGR 11-2
Modulation of extracellular matrix turnover in the trabecular meshwork
Fuchshofer R; Tamm ERExperimental Eye Research 2009; 88: 683-688
Intraocular pressure (IOP) is the most critical risk factor for primary open angle glaucoma (POAG). In most cases of POAG, IOP is increased because of an abnormally high aqueous humor outflow resistance in the juxtacanalicular region of the trabecular meshwork. A distinct structural change in the trabecular meshwork of patients with POAG is the increase in fibrillar extracellular matrix in the juxtacanalicular region of the trabecular meshwork. Our knowledge on the molecular factors that govern turnover of the extracellular matrix in the trabecular meshwork has increased considerably in recent years. It has become clear that quality and quantity of the extracellular matrix in the trabecular meshwork are regulated by several signaling molecules that interact with each other to promote its synthesis, degradation, or extracellular modification. Transforming growth factor-beta1 and beta2 (TGF-beta1 and TGF-beta2) which derive from the aqueous humor or may be locally expressed induce in cultured trabecular meshwork cells the expression of a variety of extracellular matrix molecules. The action of TGF-betas very likely requires local activation by thrombospondin-1 and is partly mediated by its downstream mediator connective tissue growth factor, both of which are constitutively expressed in the trabecular meshwork. Bone morphogenetic proteins (BMP)-7 and -4 effectively antagonize the effects of TGF-beta2 on matrix deposition. The antagonizing effects of BMP-7 are mediated in trabecular meshwork cells through Smad7. Smad7 is a key molecular switch to inhibit TGF-beta2 signaling in the trabecular meshwork.
Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany. rudolf.fuchshofer@vkl.uni-regensburg.de
Classification:
2.6.2.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics > 2.6.2 Outflow)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
