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J. Von Eicken, U. Birk, S. Grisanti, O. Denk; Inhibition of Proliferation of Cultured Human Tenon's Capsule Fibroblasts by the PDGF-receptor Specific Tyrphostin AG 1295 after Stimulation with PDGF-BB . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1189.
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Purpose: We have previously shown that PDGF-isoforms are potent stimulators of proliferation of cultured human tenon's capsule fibroblasts. In the present study we investigated the antiproliferative effects of the tyrphostin AG-1295, a PDGF-receptor-ß-specific tyrosine kinase inhibitor, on cultured human tenons capsule fibroblasts (HTF) after stimulation with PDGF-BB. Methods: HTF were grown from small tissue biopsies which were obtained during pars plana vitrectomies. Proliferation of cultured HTF upon stimulation with 50 ng/ml PDGF-BB was inhibited using increasing concentrations of AG 1295 diluted in DMSO (0.1, 1, 10, and 100 µmol/l). Cells treated with PDGF-BB and DMSO only (0.001%, 0.01%, 0.1% and 1%) served as control. The cells were harvested with trypsin/EDTA on days 1, 3, 5, 8, 10 and cell number was determined using a computer-based cell counter system (Schärfe Systems, Reutlingen, Germany). Results: Compared with the DMSO-treated controls, we observed a significant reduction of proliferation when cells were treated with 100 µmol/l AG-1295. Inhibition of PDGF-BB induced proliferation of HTF was maximal after 5 days in culture (11.2-fold). Less but still significant inhibition was found after 3 days (3.9-fold), 8 days (4.8-fold) and 10-days (3.8-fold). More over lower levels of AG-1295 induced a dose dependent inhibition. Conclusion: The results of the present study show for the first time, that AG-1295 is a potent pharmacological agent for the inhibition of PDGF-stimulated HTF cell proliferation. It may therefore serve as a therapeutical tool to inhibit the repair reaction after glaucoma filtering surgery.
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