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 mu scle actin, have been described in anterior subcapsular cataract and a fter-cataract. In a previous study in this laboratory, it was shown th at transforming growth factor-beta (TGF beta) induces the formation of spindle-shaped cells in lens epithelial explants. The aim of this inv estigation was to determine whether these TGF beta-induced spindle-sha ped 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 monitore d by phase contrast microscopy, localisation of filamentous actin with rhodamine-phalloidin, and immunolocalisation and immunoblotting of al pha-smooth muscle actin. TGF beta induced rapid cell elongation and fo rmation of characteristic spindle-shaped cells in lens epithelial expl ants in the presence or absence of FGF. These cells contained alpha-sm ooth muscle actin, a marker for myofibroblastic cells and a protein no t normally found in the lens. The present study thus provides molecula r evidence that TGF beta induces cataractous changes in lens epithelia l cells. As TGF beta is potentially available to lens cells in situ th roughout life, these findings are consistent with a key role for TGF b eta in the aetiology of major forms of subcapsular cataract.