PurposeThe mechanism by which prostaglandin(PG)F2αincreases uvcoscleral outflow and lowers intraocular pressure in primates is not known. In cultured human ciliary muscle cells, PGF2α, induces the expression of the protooncogene c-fos which is known to induce the transcription of genes such as matrix metalloproteinase-1 (MMP-1) and MMP-3 in other cell systems. As these enzymes are initially secreted as proenzymes, the present study was undertaken to determine if PG treatment induces ciliary muscle cells to secrete either proMMP-1 or proMMP-3.MethodsHuman ciliary smooth muscle cells were grown to confluence in monolayer cell cultures and then treated with PGF2α, 17-phenyltrinor-PGF2α, or 11-deoxy-PGE1. Medium harvested at various times after treatment was assayed for proMMP-1 and proMMP-3 content using sandwich ELISAs.ResultsThree days after adding 10 nM PGF2α, proMMP-1 and pro-MMP-3, concentrations in the culture medium were increased by 254±33% (mean±SE) and 128±13%, respectively. Compared with vehicle controls, 24 h treatment with 200 nM PGF2α, 17-phenyltrinor-PGF2α, or PGE1, increased proMMP-1 by 116±29%, 169±26%, and 273±16%, respectively. In parallel experiments, proMMP-3 was increased by 99±18%, 82±24%, and 214±16%, respectively.ConclusionsThese results suggest that induction of MMPsin situfollowing topical PG treatment may degrade ciliary muscle extracellular matrix and possibly contribute to increased uveoscleral outflow, as well. Curr. Eye Res. 15: 869–875, 1996.