P 14Transforming growth factor beta modulates tissue plasminogen activator expresion in human retinal glial cells
W. Schacke1, L.-O. Hattenbach1, K. F. Beck2, J. Pfeilschifter2, F. Koch1
Purpose: Plasminogen activators have been shown to play a key role in fibrinolysis, tissue destruction and remodeling, neurotoxicity and angiogenesis. Since matrix degradation is an important step in endothelial cell migration and proliferation in ocular neovascular diseases, there is much evidence that serine proteases such as tissue plasminogen activator (t-PA) are involved in this process. In this study, we investigated the role of human retinal glial cells (hRGC) as a possible source of plasminogen activators under basal conditions and after stimulation in vitro.
Methods: Levels of t-PA antigen in cell culture supernatant of hRGC were measured by ELISA under basal conditions and after exposure to transforming growth factor-beta (TGF-beta).
Results: Cultures of hRGC generated t-PA antigen under basal conditions and in a time- and dose dependent manner after exposure to stimuli. The expression of t-PA by hRGC was markedly increased after stimulation with TGF-beta.
Conclusions: The finding that hRGC can produce t-PA reflects the potential role of these cells in the progression of neovascular intraocular diseases and possibly other retinal disorders. Furthermore, our results suggest that modulation of plasminogen activator generation by hRGC is influenced by cytokines. An understanding of the endogenous inhibition of matrix degradation may be useful in the development of new treatment strategies for various diseases of the eye.
Support: August Scheidel research grant
Klinik für Augenheilkunde1 and Institut für Allgemeine Pharmakologie und Toxikologie2, Johann Wolfgang Goethe University Hospital, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main