Taxol, cytochalasin B and colchicine effects on fibroblast migration and contraction: a role in glaucoma filtration surgery?
Migration and contraction are fibroblast activities in scar tissue formation which may contribute towards the failure of trabeculectomies. We attempted to modify the migration and contraction of Tenon's capsule fibroblasts in vitro using the drugs taxol, cytochalasin B and colchicine. Migration assays were conducted in 48-well micro-chemotaxis chambers, using rabbit aqueous humour which has been previously identified as a powerful chemoattractant for Tenon's fibroblasts, and fibronectin as the stimuli for migration. All three drugs inhibited the migration of fibroblasts to both fibronectin and aqueous humour, with maximal activity seen at 10(-6)M (taxol), 10(-5)M (cytochalasin B), and 10(-3) M (colchicine). In a single cell contractile assay in which contraction of whole fibroblasts was initiated with exogenous adenosine triphosphate (ATP), taxol and colchicine showed anticontractile activity, maximal at 10(-5)M and 10(-3)M respectively, but cytochalasin B was ineffective. The significance of the activities of these drugs in relation to their proposed use for improving the success of trabeculectomies is discussed.
Joseph
J P
JP
Institute of Ophthalmology, London, UK.
Grierson
I
I
Hitchings
R A
RA
D000199:Actins / Q000276:immunology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal; D001082:Aqueous Humor / Q000378:metabolism; D002465:Cell Movement; D003078:Colchicine / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005901:Glaucoma / Q000601:surgery*; D017239:Paclitaxel; D011817:Rabbits; D014130:Trabeculectomy; D014404:Tubulin / Q000276:immunology
D000199:Actins; D000470:Alkaloids; D000911:Antibodies, Monoclonal; D005353:Fibronectins; D014404:Tubulin; D003571:Cytochalasin B; D017239:Paclitaxel; D003078:Colchicine