Purchase this article with an account.
Tomoko Orita, Kazuhiro Kimura, Koh-hei Sonoda; Role of female sex hormones in collagen gel contraction mediated by retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):380.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Contraction of collagen gels mediated by retinal pigment epithelial (RPE) cells has been studied as a model of proliferative vitreoretinopathy (PVR). The effects of sex hormones on the contractility of RPE cells cultured in a three-dementional collagen gel were investigated.
Mouse RPE cells were cultured in a type I collagen gel with 17β-estradiol, progesterone or dehydroepiandrosterone. Collagen contraction induced by transforming growth factor-β2 (TGF-β2) was evaluated by measurement of gel diameter. Expression of α-smooth muscle actin (α-SMA) as well as phosphorylation of Smad2 and myosin light chain (MLC) were examined by immunoblot analysis. Matrix metalloproteinase (MMP) release was evaluated by gelatin zymography. Fibronectin and interleukin-6 secretion were measured with immunoassays.
The female sex hormones 17β-estradiol and progesterone inhibited TGF-β2-induced collagen contraction mediated by RPE cells, whereas the male sex hormone dehydroepiandrosterone had no such effect. The TGF-β2-induced release of MMP-2 and MMP-9 from RPE cells was also inhibited by 17β-estradiol and progesterone, and the MMP inhibitor GM6001 attenuated TGF-β2-induced collagen contraction. Expression of the mesenchymal markers α-SMA and fibronectin, interleukin-6 release, and Smad2 and MLC phosphorylation induced by TGF-β2 were all inhibited by 17β-estradiol and progesterone. Immunohistochemical analysis also detected nuclear immunoreactivity for estrogen and progesterone receptors in proliferative fibrocellular membranes of PVR patients.
Female sex hormones inhibited TGF-β2-induced collagen contraction mediated by RPE cells. This action appeared to be mediated through inhibition both of MMP, α-SMA, and fibronectin expression as well as of Smad2 and MLC phosphorylation. Female sex hormones might thus inhibit progress of PVR.
This PDF is available to Subscribers Only