The effect of high-voltage electric pulses and antiproliferatie drugs on cultured rabbit subconjunctival fibroblasts

Purpose. Antiproliferative agents are currently used to inhibit Tenon's fibroblasts proliferation following glaucoma filtering surgery. This work was carried out to determine the effect of antiproliferative agents combined with high voltage electric pulses (EP) on the proliferation of Tenons' fibroblasts in rabbits. Methods. Tenon's fibroblasts in rabbits were cultured and exposed brifely to antiproliferative agents; bleomycin (BLM), mitomycin C (MMC), 5-fluorouracil (5-FU) or streptomycin (SM) either with or without high voltage electric pulses (2000V/cm, 98 μsec, 8 pulses). Cell proliferation was assessed by cell counting and a 3H-thymidine uptake assay. A morphological evaluation was performed by electron microscopy while DNA fragmentation was also assessed by a flowcytometric analysis. Results. BLM, MMC and 5-FU treatment inhibited cell proliferation in a dose dependent manner either with or without EP (p<0.05). The EP treatment augmented the inhibitory effect of BLM on cell proliferation which was 100 times more prominent than that observed for BLM treatment alone (p<0.05). BLM treatment with EP increased both apoptotic like DNA fragmentation in a flowcytometric DNA histogram and nuclear condensation based on the findings of morphological analysis. Conclusions. EP treatment augmented the inhibitory effect of BLM on cell proliferation. The combined effect of electric pulse and antiproliferative agent treatment was thus found to reduce the required dose of antiproliferative agent thus helping to make glaucoma filtering surgery substantially safer and more effective than antiproliferative agent treatment alone.