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J Von Eicken, S Grisanti, PO Denk; Inhibition of proliferation of cultured human Tenon's capsule fibroblasts by the PDGF-receptor specific tyrphostin AG 1295 . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3360.
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Purpose: Tyrphostins are low molecular weight inhibitors of protein tyrosine kinases. In the present study we investigated the antiproliferative effects of the PDGF-receptor-ß-specific tyrphostin AG-1295 on cultured human tenons capsule fibroblasts (HTF). Methods: Inhibition of the phosphorylation of the PDGF-receptor type beta was investigated after treatment of cultured HTF with AG 1295, AG 9 and DMSO 0.1% (negative control) and subsequent stimulation with PDGF-BB (10ng/ml) using Western Blot techniques. The effect of AG 1295 on serum-induced proliferation of cultured HTF was investigated using different concentrations of AG 1295 (0.1, 1, 10, and 100 µmol/l) and DMSO (0.001%, 0.01%, 0.1% and 1%). The cells were harvested with trypsin/ EDTA on days 1, 3, 5, 8, 12 for counting. Results: We were able to detect a significant reduction of phosphorylation of PDGF-receptor type beta after treatment with AG-1295 when compared to DMSO only in the immunoblots. Furthermore, preliminary results of the proliferation assays show that the addition of 10 and 100 µmol/l AG-1295 to cultures of HTF result in an inhibition of proliferation when compared with the DMSO treated control cells after 5 and 8 days in culture. Conclusion: The results of the present study suggest, that AG-1295 is able to inhibit HTF cell growth stimulated by 10% FCS. Tyrphostins may serve as therapeutical tools for the inhibition of wound healing after glaucoma filtering surgery.
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