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C.M. Garcia, K. Kang, S. Jin, I. Lee, D.C. Beebe; The Effect of BMP–7 and the PPAR– Agonists, Troglitazone and GW1929 on Lens Myofibroblast Formation in vitro . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4321.
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© ARVO (1962-2015); The Authors (2016-present)
Secondary cataracts form by the transdifferentiation of lens epithelial cells into myofibroblasts. TGF–ß has been implicated as a major player in myofibroblast formation. However, in other tissues, fibrosis can be inhibited by other growth factors, such as BMP–7, or by agonists of the nuclear hormone receptor, peroxisome proliferator–activated receptor–γ (PPARγ). We used lens epithelial cell explants to test whether BMP–7 or the PPARγ agonists, troglitazone or GW1929, were able to inhibit lens fibrosis.
Lens epithelial cell explants from adult BALBc mice were cultured in 0.1% BSA/DMEM, in the presence or absence of BMP–7 (50–100 ng/ml) or the PPARγ agonists, troglitazone (10 µM) or GW1929 (10 µM). Explants were harvested for Western blot analysis and immunohistochemistry immediately after explantation or after 4 days of culture. An antibody to α–smooth muscle actin (α–SMA), a marker of myofibroblasts, was used to compare levels of fibrosis in the treated and non–treated explants.
At the time of explantation, lens epithelial cells expressed low levels of α–SMA. α–SMA levels increased ∼12 fold after 4 days in culture. Treatment of lens explants with troglitazone decreased α–SMA levels by an average of 82%, compared to untreated explants (p < 0.05). In two of the three trials, troglitazone completely suppressed the culture–induced increase in the α–SMA level. Results with BMP–7 and GW1929 were more variable than with troglitazone. These treatments reduced α–SMA levels by an average of only 28% and 39%, respectively, compared to non–treated explants.
Troglitazone effectively reduced α–SMA accumulation in vitro. Understanding the mechanisms by which this PPARγ agonist suppresses fibrosis may be useful for the prevention of secondary cataracts, especially since this class of drugs is already approved for use in humans.
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