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Jayter Silva Paula, Carolina Maria Modulo, Eduardo M Rocha, Peter S Reinach, Marco Andrey C Frade; Losartan efficacy in supressing responses contributing to fibrosis in TGF-beta-stimulated Tenon's fibroblasts. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3204.
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© ARVO (1962-2015); The Authors (2016-present)
Collagen deposition and myofibroblast differentiation are key factors related to excessive subconjunctival scarring observed frequently after glaucoma filtration surgery. We described in 2013 at the ARVO meeting that Losartan potassium (LP), an angiotensin-1 receptor antagonist, decreases myofibroblast differentiation in rabbit Tenon’s capsule fibroblasts (RTF). We now determined if LP also suppresses fibrosis factors in transforming growth factor (TGF-beta-2) stimulated RTF.
Fibroblasts obtained from New Zealand rabbits were cultured in Dulbecco's modified Eagle's medium (DMEM). At the third passage, RTF was incubated with recombinant TGF-beta2 5ng/ml for 48 h, before being treated with LT. The dose dependent effects of LP (i.e. 0.3, 1.0 and 3.0 μM) were determined in triplicate after 24 h and 48 h with the MTT assay. Real-time reverse transcription polymerase chain reaction evaluated type I alpha I collagen (COL1A1) and TGF-beta2 gene expression.
LP induced, in a dose dependent fashion, declines in RTF proliferation in the absence of TGF-beta2. However, only 1.0 μM (p=0.0240; at 24 h) and 3.0 μM LP (p=0.0062 and p=0.0239; at 24 h and 48 h, respectively) inhibited rises in proliferation induced by TGF-beta2. TGF-beta2 incubation induced a five-fold increase in COL1A1 expression (p=0.021). Although all LT concentrations suppressed COL1A1 mRNA expression in the absence of TGF-beta-2 at 24 h, LT did not decrease significantly its expression after TGF-beta2- exposure for either 24 h and 48 h. TGF-beta2 mRNA expression remained unchanged irrespective of the absence or presence of TGF-beta-2.
TGF-beta2 reduced declines in RTF proliferation observed with LP treatment. Although LP decreased COL1A1 gene expression at 24 h in the absence of TGF-beta2, in the presence of TGF-beta2 LP had no effect on both this response and TGF-beta2 expression. The present work suggests that LP may not be effective in modulating TGF-beta2-stimulated RTF, but it may still be somewhat useful as an adjunctive agent in glaucoma surgery by preventing RTF proliferation.
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