EFFECTS OF SINGLE EXPOSURES TO ANTIPROLIFERATIVE AGENTS ON OCULAR FIBROBLAST-MEDIATED COLLAGEN CONTRACTION

Purpose. To determine the effects of short-duration treatments with 5- fluorouracil (5FU) and mitomycin-c (MMC) on ''activated'' and ''nonact ivated'' ocular fibroblasts in collagen lattices. Methods. Activated a nd nonactivated ocular fibroblasts seeded in collagen lattices were ex posed to single 5-minute treatments with 5FU (0.01 to 25 mg/ml) and MM C (0.01 to 1 mg/ml). The effects of these treatments on lattice contra ction, cellularity, cellular viability, cellular structure, and actin distribution were investigated. Results. Treatment with 5FU (0.01 to 2 5 mg/ml) or MMC (0.1 to 1 mg/ml) significantly inhibited (P < 0.001 an d P < 0.0001, respectively) lattice contraction compared to water cont rols. The degree of inhibition was greater in lattices containing nona ctivated cells than in those containing activated cells. Activated cel l viability and cellularity, unlike their nonactivated counterparts, w ere not significantly affected (P > 0.0083) by treatment with 5FU at h igh concentrations (25 mg/ml). MMC treatment had significant effects o n cell viability and cellularity (P < 0.0001). Treatment with 5FU and MMC also affected cellular structure and actin distribution compared t o water controls. Conclusions. Single, short exposures to 5FU or MMC i nhibit ocular fibroblast-mediated collagen contraction. MMC causes cel l death and a decrease in cellularity at high concentrations. The resu lts also indicate that collagen lattices seeded with activated and non activated fibroblasts are differentially affected by short-term exposu res to 5FU or MMC. These findings may have important clinical implicat ions regarding the concentrations of these agents used in the treatmen t of different patient groups.