o-(chloroacetylcarbamoyl)fumagillol and Pterygium

To study drug therapy for pterygium, especially the effect of a fumagillin analog, TNP-470, a potent anti-angiogenic compound, on the growth of cultured fibroblasts obtained from primary pterygia and normal human conjunctiva.. Cultured pterygium fibroblasts (PF) were exposed to different concentrations of TNP-470 every other day for 7 days (Treatment A) and to a single dose before 4 days of culture (Treatment B). Human normal conjunctival fibroblasts (HCF) were treated with TNP-470 every other day for 7 days. The cells were observed daily by phase contrast microscopy. Cell proliferation was assessed by counting cells with a hemocytometer. Trypan blue uptake was used to determine cell viability at harvest.. TNP-470 induced a significant inhibition of PF and HCF proliferation in a dose-dependent manner (P < .0001). At the lowest dose of TNP-470 (100 pg/ml), the cumulative inhibitory effect of TNP-470 was more potent than the sustained inhibitory effect observed by treatment B in one high dose. Nevertheless, the cytotoxic effect was dose-dependent and more marked after treatment A than after treatment B. After washing out of the drug, partial reversibility was observed at doses lower than 5 mg/ml with a significant increase of viability. HCF were less sensitive to TNP-470 and doses less than 5 mg/ml were not cytotoxic.. TNP-470 appears to have a marked inhibitory effect on PF proliferation, and it may be of considerable value in the prevention of pterygium growth and recurrence.

Topics: Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Cell Division; Cell Survival; Cells, Cultured; Conjunctiva; Cyclohexanes; Dose-Response Relationship, Drug; Female; Fibroblasts; Humans; Male; Microscopy, Phase-Contrast; Middle Aged; O-(Chloroacetylcarbamoyl)fumagillol; Pterygium; Sesquiterpenes