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A. Ohlmann, C. Flügel-Koch, U. Welge-Lüssen, E.R. Tamm; Thrombospondin-1 Is Expressed in the Trabecular Meshwork In Situ and In Vitro, and Is Regulated by TGF-Beta and Dexamethasone . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1175.
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Purpose: To study localization and expression of thrombospondin-1 (TSP-1) in the trabecular meshwork (TM) in situ and in vitro. Thrombospondin-1 (TSP-1) is an extracellular matrix protein that belongs to the group of matricellular proteins, which have important cell regulatory properties. TSP-1 has been shown to influence cell adhesion, proliferation and angiogenesis. In addition, TSP-1 is a potent endogenous activator of extracellular transforming growth factor-ß (TGF-ß). TGF-ß is found at high levels in the aqueous humor (AH), which are elevated in patients with POAG. Most of the TGF-ß in the AH is present in a latent, inactive form. Methods: TSP-1 immunohistochemistry was performed in the eyes of human donors (5 normal and 12 with POAG), and in normal and TSP-1 knockout mice. TSP-1 expression was assessed by RT-PCR and northern blotting in mRNA from fresh TM, and human and murine TM (MUTM-NEI/1) cells in vitro. In addition, northern and western blot analyses of TM cells after incubation with TGF-ß1 and dexamethasone were performed. Results: In both human and mouse eyes, intense TSP-1 immunolabeling was observed throughout all layers of the TM, while other ocular tissues showed no or only weak labeling. TSP-1 staining was seen in TM cells, and in the extracellular matrix of trabecular lamellae and JCT. TSP-1 staining did colocalize with that of fibronectin in the JCT, but not with that of type VI collagen. In 5 eyes with POAG, TSP-1 labeling was more intense than in normals. No TSP-1 staining was seen in TSP-knockout mice which showed no obvious TM phenotype. mRNA for TSP-1 was detected both in fresh and cultured TM cells. Incubation of TM cells with TGF-ß1 and dexamethasone caused a marked increase in TSP-1 expression. Conclusions: TSP-1 in the TM might act as a potent local endogenous activator of TGF-ß in the aqueous humor and mediate any local effects of TGF-ß and/or dexamethasone on the outflow tissues. In addition, it might be involved in other important aspects of TM biology.
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