TGF-beta 1 induces lens cells to accumulate alpha-smooth muscle actin, a marker for subcapsular cataracts

Spindle-shaped myofibroblast-like cells, which contain alpha-smooth muscle actin, have been described in anterior subcapsular cataract and after-cataract. In a previous study in this laboratory, it was shown that transforming growth factor-beta (TGF beta) induces the formation of spindle-shaped cells in lens epithelial explants. The aim of this investigation was to determine whether these TGF beta-induced spindle-shaped cells contain alpha-smooth muscle actin. Lens epithelial explants were prepared from 21-day-old rats and cultured with either TGF beta 1 or basic FGF alone, a combination of both growth factors, or without added growth factors. After three days, cellular changes were monitored by phase contrast microscopy, localisation of filamentous actin with rhodamine-phalloidin, and immunolocalisation and immunoblotting of alpha-smooth muscle actin. TGF beta induced rapid cell elongation and formation of characteristic spindle-shaped cells in lens epithelial explants in the presence or absence of FGF. These cells contained alpha-smooth muscle actin, a marker for myofibroblastic cells and a protein not normally found in the lens. The present study thus provides molecular evidence that TGF beta induces cataractous changes in lens epithelial cells. As TGF beta is potentially available to lens cells in situ throughout life, these findings are consistent with a key role for TGF beta in the aetiology of major forms of subcapsular cataract.