IN-VITRO INHIBITION OF COLLAGEN FORMATION BY 2,4-PYRIDINE DICARBOXYLATE AND MINOXIDIL IN RABBIT CORNEAL FIBROBLASTS

Two anti-fibrotic agents were evaluated in vitro for potential applica tion in trabeculectomy. The rate of collagen formation by cultured rab bit corneal fibroblasts was determined by [H-3]proline uptake and hydr oxylation assay. Incubation of fibroblasts, for 96 hours, with 16 mM 2 ,4-pyridine dicarboxylic acid (2,4-PDCA), a competitive inhibitor of p rolyl 4-hydroxylase, decreased [H-3]OH-proline formation from control by 28.2+/-3.9%; (average+/-S.E.M), whereas 10 mM minoxidil, an antihyp ertensive pyrimidine oxide and a lysyl hydroxylase inhibitor, induced a decrease of 17.3+/-4.5%. Incubating fibroblasts with a mixture of th e two inhibitors, 16 mM 2,4-PDCA and 10 mM minoxidil, resulted in a fu rther decrease in [ H]proline incorporation of 40.7+/-5.1%. After 96 h ours of incubation with the inhibitors, rabbit corneal fibroblast grow th was decreased from control by 17.2+/-4.2% and 10.5+/-4.5% for 16 mM 2,4-PDCA and 10 mM minoxidil, respectively. These effects were dose d ependent. The results suggest that both 2,4-PDCA and minoxidil have an inhibitory effect on collagen formation and may be useful in delaying surgical wound healing.