Abstract
BackgroundDifferences in the increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) activity may contribute to the different characteristics observed clinically on decreased intraocular pressure in patients with glaucoma or ocular hypertension. The purpose of this study was to investigate differences in the expression profiles of MMPs and TIMPs induced by the prostaglandin analogs bimatoprost, latanoprost, and tafluprost in human non-pigmented ciliary epithelial cells (HNPCECs).MethodsHNPCECs were cultured for 24 h with 0, 10, 100, or 1000 μM of the free acid forms of bimatoprost, latanoprost, and tafluprost. We measured the expression levels of MMPs and TIMPs using real-time polymerase chain reaction, and compared the results. Enzyme activities of MMP-2 and −9 in conditioned media were measured by gelatin zymography.ResultsAll prostaglandin analogs we examined dose-dependently increased expression levels of MMP-1, −2, −3, −9, and −17, whereas expression levels of TIMP-1 and −2 decreased with increasing concentrations of each analog. Each prostaglandin analog induced different levels of increases in MMPs and decreases in TIMPs.ConclusionsUnique expression profiles of MMPs and TIMPs induced by bimatoprost, latanoprost, and tafluprost, as shown in HNPCECs, may contribute to clinically different effects on intraocular pressure decreases in patients with glaucoma or ocular hypertension.
Highlights
Differences in the increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) activity may contribute to the different characteristics observed clinically on decreased intraocular pressure in patients with glaucoma or ocular hypertension
The qPCR results demonstrated that MMP-1, MMP-2, MMP-3, MMP-9, and MMP-17 mRNA expression levels were dose dependently increased with increasing bimatoprost, latanoprost, or tafluprost concentrations (Fig. 1, Table 1)
When the concentrations of the prostaglandin analog (PGA) were 1000 μM, the MMP-1, MMP-2, MMP-3, MMP-9, and MMP-17 expression levels significantly increased compared to the control levels
Summary
Differences in the increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) activity may contribute to the different characteristics observed clinically on decreased intraocular pressure in patients with glaucoma or ocular hypertension. The purpose of this study was to investigate differences in the expression profiles of MMPs and TIMPs induced by the prostaglandin analogs bimatoprost, latanoprost, and tafluprost in human non-pigmented ciliary epithelial cells (HNPCECs). Bimatoprost (amide prodrug of 17-phenyl-PGF2α), latanoprost (ester prodrug of PGF2α), and tafluprost (difluoroprostaglandin derivative of PGF2α) are prostaglandin analogs (PGAs) available for clinical use to lower patients’ intraocular pressure (IOP). Previous studies reported differential expression of MMPs in the ciliary body or ciliary muscle after bimatoprost, latanoprost, or tafluprost treatment [2,3,4, 7].
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