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Georges Kalouche, Michael Bakria, Celine Boucher, Patrick Avenet, Stephane Melik-Parsadaniantz, Caroline Leriche, Thomas Debeir, Xavier Vige, Christophe Baudouin, William H Rostene; Latanoprost prevents TGF-β2-induced collagen deposition and promotes contraction in trabecular meshwork cells.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):554.
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© ARVO (1962-2015); The Authors (2016-present)
Latanoprost is the first-line medication in the treatment of glaucoma but its direct action on the trabecular meshwork (TM), the main site of resistance to the aqueous humor outflow, is still controversial. In this study, the authors examined the effects of latanoprost on collagen accumulation and contraction of human TM cells.
Primary human TM cells were pretreated with vehicle (DMSO 0.1%) or latanoprost acid (1 µM) and incubated with TGF-β2 (2 ng/ml). After 96h, collagen I, F-actin and phospho-myosin light chain (p-MLC) immunolabelings were analyzed by quantitative immunocytochemistry. Total RNA from treated TM cells were isolated at 6, 24 and 48h, and qPCR were performed to detect the mRNA of collagen 1(Col1A1), metalloproteinase (MMP)-1, and lysyl oxidase (LOX).
TGF-β2 induces a deposition of collagen I in TM cell culture which is inhibited by latanoprost (p<0.01). Batimastat, a broad spectrum MMP inhibitor, does not prevent the latanoprost-dependent inhibition of collagen deposition. Furthermore, TGF-β2 time-dependently up-regulates collagen I, LOX and MMP-1 mRNA expressions which are not modulated by pretreatment with latanoprost. In addition, latanoprost induces a time-dependent contraction of TM cells as evidenced by an increased staining for F-actin and p-MLC. Latanoprost does not potentiate the TGF-β2-dependent increased in F-actin staining.
Latanoprost inhibits collagen deposition induced by TGF-β2 in a MMP independent manner. mRNA of collagen I, LOX and MMP-1, respectively involved in collagen degradation and cross-linking, are not modulated by latanoprost. These results suggest that latanoprost can act on the TM by decreasing collagen deposition independently of MMPs as opposed to its effects on uveoscleral tissues. However, latanoprost by activating the actomyosin system seems to induce a concomitant contraction of TM cells which could antagonize its intraocular pressure (IOP) lowering effect. Further studies would evaluate the contribution of latanoprost-dependent TM cells contraction on IOP.
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