IN-VITRO EVALUATION OF ANTIPROLIFERATIVE POTENTIAL OF CALCIUM-CHANNELBLOCKERS IN HUMAN TENONS FIBROBLASTS

The calcium cation has been known to play a central and diverse role i n the proliferation of numerous types of cells including fibroblasts. Therefore, it follows that calcium channel blockers (CCBs) may potenti ally inhibit fibroblast attachment and proliferation. The time and dos e-related effects of fine commonly used CCBs-verapamil, diltiazem, nic ardipine, trifluoperazine, and dantrolene-on human Tenon's fibroblast attachment and proliferation were studied. Fibroblasts were incubated with different concentrations of each drug. To evaluate the effect of each drug on fibroblast attachment, cell density was quantified by Cou lter counter and hexosaminidase assays after 24 hours of incubation. T o evaluate the effect of each drug on fibroblast proliferation, cell d ensity was quantified by Coulter counter, hexosaminidase, and H-3-thym idine uptake assays on days 1, 3, and 7. Dantrolene had minimal effect , failing to cause even 20% inhibition at 10(-5) M, the highest concen tration tested. Verapamil, diltiazem, nicardipine, and trifluoperazine all inhibited fibroblast attachment and proliferation. Trifluoperazin e was the most potent inhibitor of attachment and proliferation with I D(50)s in the 10(-5) M range. Verapamil, diltiazem, and nicardipine ha d similar potency in inhibiting attachment and proliferation with ID(5 0)s in the 10(-4) M range. Because CCBs seem to inhibit fibroblast att achment and proliferation, future clinical studies may show that these agents reduce collagen production, scar formation, and bleb failure f ollowing glaucoma filtration surgery. (C) 1997 Academic Press Limited.