TNP-470 (a fungus-derived inhibitor of angiogenesis) reduces proliferation of cultured fibroblasts isolated from primary pterygia: a possible drug therapy for pterygia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kria
L
L
Department of Ophthalmology, Nagasaki University School of Medicine, Japan.
Ohira
A
A
Amemiya
T
T
D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects; D003510:Cyclohexanes; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D008858:Microscopy, Phase-Contrast; D008875:Middle Aged; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011625:Pterygium / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol