In vitro evaluation of antiproliferative potential of topical cyclooxygenase inhibitors in human Tenon's fibroblasts.
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.
Nguyen
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Jules Stein Eye Institute, Los Angeles, CA 90024-7004.
Lee
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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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D010894:Piroxicam; D004008:Diclofenac; D005480:Flurbiprofen; D013496:Suprofen