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M. Angert, J.D. Lindsey, R.N. Weinreb; Exposure of Human Sclera Increases Matrix Metalloproteinase-1 Gene Transcription . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4415.
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Purpose: Exposure of isolated human sclera to latanoprost acid in vitro increases transscleral permeability and secretion of matrix metalloproteinase-1 (interstitial collagenase, MMP-1). The present study was undertaken to compare latanoprost-mediated induction of the mRNA for MMP-1 in scleral pieces isolated from human donor eyes. Methods: Multiple scleral pieces approximately 1 cm2 in size were dissected from six postmortem human eyes and placed into individual organ cultures. Parallel cultures from the same eye were then treated for 24 hours with medium supplemented with vehicle or 100 nM latanoprost acid. The cDNA samples from the control and treated cultures were evaluated for MMP-1 and GAPDH mRNA content by real-time PCR analysis. Results for MMP-1 mRNA were normalized according to GAPDH mRNA in each sample. Results: MMP-1 mRNA was increased by latanoprost treatment in cultures generated from four of the six eyes by 1.3±0.2-fold, 1.4± 0.2-fold, 2.8±0.5-fold, and 3.3±1.0-fold. MMP-1 mRNA differed insignificantly from the control cultures in the treated cultures from the other two eyes. Conclusions: There appears to be individual variability in the influence of latanoprost treatment on MMP-1 gene transcription in postmortem human sclera organ cultures. Although the basis of this variability is not known, these results suggest that the increased scleral MMP-1 observed in sclera following topical latanoprost originates in part from local biosynthesis.
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