Expression of the TGF-b Activating Molecule Thrombospondin-1 in the Trabecular Meshwork

¹Ohlmann A., ¹Flügel-Koch C., ²Tamm E.,
¹Friedrich-Alexander-Universität, Institut für Anatomie, Molekulare Anatomie & Embryologie (Erlangen)
²Friedrich-Alexander-Universität, Anatomisches Institut, Molekulare Anatomie und Embryologie (Erlangen)

Purpose: In glaucomatous eyes, aqueous humor contains increased levels of transforming growth factor-β2 (TGF-β2). Most, if not all TGF-b2 in the aqueous humor is present in a latent, inactive form. Only little is known where and if TGF-β2 is activated in the anterior eye. Since thrombospondin-1 (TSP-1) is known to be a potent endogenous activator of TGF-β2, we investigated the expression of TSP-1 in the human and mouse eye.
Method: Normal and glaucomatous human eyes as well as normal and TSP-1 deficient mice eyes were examined by immunohistochemistry and RT-PCR. In addition northern and western blot analyses of cultured human trabecular meshwork cells were performed.
Results: In human and mouse eyes, the trabecular meshwork (TM) was intensely labelled for TSP-1. A weak signal for TSP-1 was observed in Bruch´s and Descemet´s membranes. TSP-1 deficient mice that were used as negative controls, showed no immunostaining for TSP-1. No differences in TSP-1 localization was observed between normal human eyes and those with primary open angle glaucoma (POAG). In cultured human trabecular meshwork cells, an expression of TSP-1 was seen in western and northern blot analyses. After incubation of the cells with activated TGF-β1, an increase in mRNA for TSP-1 was observed.
Conclusions: TSP-1 in the TM might act as a potent activator of TGF-β2 in the aqueous humor and mediate any local effects of TGF-β2 on the outflow tissues in normal eyes and those with POAG.

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