Effect of steroids and nonsteroidal antiinflammatory agents on human ocular fibroblast.
5-fluorouracil and steroids have been used to suppress excessive scar formation after glaucoma filtering surgery (GFS). Steroidal and nonsteroidal antiinflammatory drugs (NSAIDs), which are inhibitors of arachidonic acid (AA) pathway, both limit fibroblast activity and reduce inflammation. In this experiment, the ability of corticosteroid (dexamethasone sodium phosphate), cyclooxygenase inhibitor (piroxicam), lipoxygenase inhibitor (ferulic acid), and dual cyclo/lipoxygenase inhibitor (phenidone) to inhibit human Tenon's fibroblast proliferation was evaluated in culture. After human Tenon's fibroblast cell lines were established, a complete dose-response curve was done for the representative compounds for 8 days. Fibroblast attachment and proliferation were quantified by Coulter counter, hexosaminidase, and tritiated thymidine uptake assays. All four drugs inhibited attachment and proliferation at high concentrations. Phenidone was the most effective, with inhibition occurring within the 0.001-0.1 mmol/l range. It also was the only drug that showed inhibition at the antiinflammatory range in vivo. Dexamethasone, piroxicam, and ferulic acid did not inhibit fibroblast attachment and proliferation until doses well above those required to inhibit AA biosynthesis were attained. Only dexamethasone showed increased potency with incubation time. Overall, the NSAIDs showed antiproliferative activity comparable to or better than that of the steroids. Because the potency of steroids increases over time, these drugs may be more beneficial if given prior to initiation of inflammation. These results suggest that NSAIDs may be useful as both antiinflammatory and antiproliferative agents in preventing bleb failure after GFS.
Nguyen
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Jules Stein Eye Institute, UCLA School of Medicine 90024-7004.
Lee
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DA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003373:Coumaric Acids / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005123:Eye / Q000166:cytology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003373:Coumaric Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D010894:Piroxicam; D003907:Dexamethasone; C004999:ferulic acid; D001619:beta-N-Acetylhexosaminidases; C015429:phenidone