mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells

We examined the effects of mTOR inhibitors on the fibrotic response induced by transforming growth factor-beta2 (TGF-beta 2) in cultured human trabecular meshwork (hTM) cells. TGF-beta 2-induced expression of fibronectin, collagen type I, alpha 1 chain (COL1A1), and alpha-smooth muscle actin (alpha SMA) in hTM cells was examined in the presence or absence of mTOR inhibitors using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The migration rates of hTM cells were examined in the presence of TGF-beta 2 with or without mTOR inhibitors. An in vitro study showed that the expression of fibronectin, COL1A1, and alpha SMA was upregulated by TGF-beta 2 treatment of hTM cells; such upregulation was significantly suppressed by mTOR inhibitors. The inhibitors significantly reduced the migration rate of TGF-beta 2-stimulated hTM cells. mTOR inhibitors may usefully reduce the fibrotic response of hTM cells and we may have to explore if it is also effective in in vivo model.

Automated summary

mTOR inhibitors effectively reduce the fibrotic response induced by TGF-beta 2 in cultured human trabecular meshwork cells, as well as decreasing the migration rate of the cells. Further studies are needed to explore the effectiveness of these inhibitors in in vivo models.