P 510
Inhibition of PDGF-induced proliferation of cultured human Tenon´s capsule fibroblasts by calcium-channel blockers
M. Knorr, P. O. Denk
Introduction: The wound healing response after glaucoma filtration surgery depends on the action of cytokines. Based on recent reports demonstrating that platelet-derived growth factor (PDGF) is one of the most potent stimulators of human Tenon´s capsule fibroblasts (HTF) and studies showing an inhibitory effect of calcium channel blockers (CCB) on the proliferation of HTF, the purpose of the present investigation was to evaluate the inhibitory effect of CCB on PDGF-induced proliferation of HTF.
Methods: HTF (2nd passage) were co-stimulated with PDGF-AB at a fixed concentration of 10 ng and varying concentrations (10-8-10-3 M) of 3 different CCB (verapamil, diltiazem, nifedipine). The effect of these CCBs on adhesion, cell viability and proliferation were determined using a computer-based cell counting system (CASEY 1, Schärfe System) after an incubation time of 1, 3 and 5 days.
Results: Addition of CCBs led to a significant, dose-dependent inhibition of both adhesion and PDGF-AB-induced proliferation of HTF. Verapamil, nifedipine and diltiazem revealed a pronounced inhibition of adhesion (44.8-62.1% at 10-3 M). Verapamil was the most potent inhibitor of cell proliferation with a maximal inhibition of 66.8% (day 5) at a concentration of 10-3 M and an IC50 value of 10-5.3 M. Maximal inhibitory effect of nifedipine and diltiazem were calculated to be 10-4.7 M and 10-4.8 M, respectively. Only minimal cytotoxic effects could be observed.
Conclusion: Inhibition of PDGF-induced proliferation has been identified as one possible mechanism by which CCBs reduce proliferation of HTF. Additionally, our results support the idea that application of CCB might be a useful tool in the pharmacological prevention of postoperative scarring.
University Eye Clinic Tübingen, Dept. I, Schleichstr. 12, D-72076 Tübingen