title: In vitro evaluation of antiproliferative potential of topical cyclooxygenase inhibitors in human Tenon's fibroblasts.
abstract: Pharmacologic agents which inhibit fibroblast proliferation and scar formation may improve the success of glaucoma filtration surgery. To evaluate the potential use of nonsteroidal anti-inflammatory drugs as an antifibrotic treatment following glaucoma filtration surgery, the time and dose-related effects of four commonly used topical cyclo-oxygenase inhibitors--diclofenac, flurbiprofen, piroxicam, and suprofen--on human Tenon's fibroblast attachment and proliferation were studied. Fibroblasts were incubated with different concentrations of a drug and analysed for dose response 1, 3, and 8 days following drug addition. The cell density was quantified by Coulter counting, hexosaminidase assay, and [3H]thymidine uptake into the DNA. All four drugs inhibited fibroblast attachment at the highest concentrations. Diclofenac was the most effective agent in inhibiting fibroblast proliferation, with inhibition occurring at a range of concentrations above 10(-3)-10(-4) mmol l-1. Flurbiprofen, piroxicam, and suprofen were comparable to each other in their antiproliferative activities, with inhibition occurring at a range of concentrations above 10(-1)-10(-2) mmol l-1. These results suggest a potential role for the commonly used topical nonsteroidal anti-inflammatory drugs in preventing excessive fibroblast proliferation following GFS, but further clinical studies are indicated to assess their activity as anti-inflammatory and antiproliferative agents in preventing bleb failure.
authors.affiliation: Jules Stein Eye Institute, Los Angeles, CA 90024-7004.
authors.forename: K D
authors.initials: KD
authors.lastname: Nguyen
authors.forename: D A
authors.initials: DA
authors.lastname: Lee
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D005123:Eye / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D010894:Piroxicam / Q000494:pharmacology; D013496:Suprofen / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D010894:Piroxicam; D004008:Diclofenac; D005480:Flurbiprofen; D013496:Suprofen