Pharmacological modulation of human subconjunctival fibroblast behavior in vitro.
The response of human subconjunctival fibroblasts to a variety of pharmacological agents was evaluated utilizing a novel in vitro wound assay and a separate proliferation assay. Both colchicine and cytochalasin B dramatically arrested wound closure at concentrations greater than or equal to 0.01 micrograms/ml and 2 micrograms/ml, respectively (p less than 0.05). At lower doses these drugs altered fibroblast morphology and inhibited directed cell migration. Dexamethasone and 6-MP delayed wound closure at concentrations greater than or equal to 100 micrograms/ml and 1000 micrograms/ml, respectively (p less than 0.05). Effective antiproliferative agents, in order of decreasing potency (based on unit weight), were Cytarabine (cytosine arabinoside), doxorubicin (Adriamycin), colchicine, 5-fluorouracil, cytochalasin B, cyclosporin (Sandimmune), 6-mercaptopurine, and dexamethasone. The antiprotease agents and methotrexate were ineffective as determined by both assays. We conclude that the wound assay is well suited for rapid screening of drugs for their effect on fibroblast morphology, motility, and proliferation, and that colchicine and cytochalasin B, in doses well below those documented to produce ocular toxicity, are effective in inhibiting directed migration and proliferation of subconjunctival fibroblasts in vitro. Differences in mechanism, onset of action, therapeutic range, and cytotoxicity of drugs could be exploited in controlling ocular fibroblast behavior in vivo.
Damji
K F
KF
Eye Care Center, Vancouver General Hospital, Canada.
Rootman
J
J
Palcic
B
B
Thurston
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D003078:Colchicine / Q000494:pharmacology; D003228:Conjunctiva / Q000166:cytology*; D003524:Cyclosporins / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
D000970:Antineoplastic Agents; D003524:Cyclosporins; D011480:Protease Inhibitors; D003571:Cytochalasin B; D003907:Dexamethasone; D003078:Colchicine