IN-VITRO EFFECTS OF DOXORUBICIN AND MITOMYCIN-C ON HUMAN TENONS CAPSULE FIBROBLASTS

Doxorubicin is an antiproliferative agent, that also inhibits prolyl 4 -hydroxylase in vitro. We evaluated the effects of doxorubicin and mit omycin C (MMC) on the proliferation of human Tenon's capsule fibroblas ts and the secretion of type I collagen in these cells to explore the potential use of doxorubicin as an antifibrotic agent after glaucoma f iltering surgery, Standard immunoassays were used to determine the con centrations of type I procollagen COOH-terminal peptide (PIP), laminin and vitronectin receptor in conditioned media and cell lysates in the presence or absence of doxorubicin or MMC, The mitotic activity and v iability of these cells were also determined, Cellular ultrastructure was evaluated by transmission electron microscopy, Doxorubicin and MMC decreased the cellular viability, the mitotic activity, and the produ ction of the peptides measured. The inhibition of PIP secretion into t he culture medium was higher in doxorubicin-treated cultures than in M MC-treated cultures at the tested concentrations (5-100 mu M). The dec rease in PIP levels in cell lysates was less in doxorubicin-treated cu lture (25 mu M) than in MMC-treated culture (25 mu M), suggesting that procollagen synthesis and secretion might be attenuated by doxorubici n. Ultrastructural studies revealed increased numbers of lysosomes in the cytoplasm of doxorubicin-treated cells relative to MMC-treated cel ls, Doxorubicin and MMC reduced cell viability and inhibited the proli feration and synthesis of PIP, laminin, and vitronectin receptor pepti de, Inhibitory effects of doxorubicin on PIP secretion were more poten t than those of MMC, Doxorubicin may be useful for inhibiting the fibr otic response at the site of ocular filtering surgery.