Angela M. Hales

TGF-β1 induces lens cells to accumulate α-smooth muscle actin, a marker for subcapsular cataracts

Spindle-shaped myofibroblast-like cells, which contain α-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-β (TGFβ) induces the formation of spindle-shaped cells in lens epithelial explants. The aim of this investigation was to determine whether these TGFβ-induced spindle-shaped cells contain α-smooth muscle actin. Lens epithelial explants were prepared from 21-day-old rats and cultured with either TGFβ1 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 α-smooth muscle actin.TGFβ 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 α-smooth mu...

TGFβ induces morphological and molecular changes similar to human anterior subcapsular cataract

Background: Transforming growth factor β (TGFβ) has been shown to induce subcapsular plaques in cultured rat lenses as well as in lenses of transgenic mice. In the present study the authors have extended their analysis of these cataract models to determine how closely they mimic human cataract. In particular, they studied the maturation of cataract in the transgenic model to determine if it develops similar features as previously described for anterior subcapsular cataract (ASC) in humans. Furthermore, they investigated whether both of these animal models express the range of molecular markers that have now been shown to be present in human ASC. Methods: Histology and periodic acid Schiff staining were used to study the development and maturation of subcapsular plaques in transgenic mice overexpressing TGFβ1 in the lens. Immunolabelling methods were used to identify the molecular markers for ASC in both the transgenic mouse model and in rat lenses cultured with TGFβ2. Results: Histological analysis showed that the subcapsular plaques that develop in adult transgenic mouse lenses bear a striking similarity to mature human ASC, including the formation of a new epithelial-like layer extending between the subcapsular plaque and the underlying fibre mass. All known molecular markers for human ASC were induced in both rodent models, including collagen types I and III, tenascin, and fibronectin. They also identified the presence of desmin in these plaques, a putative novel marker for human cataract. Conclusions: In both transgenic mouse and rat lens culture models TGFβ induces markers similar to those found in human ASC. Atypical expression of these cataract markers is also characteristic of posterior capsular opacification (PCO). The molecular markers expressed are typical of a myofibroblastic/fibroblastic phenotype and suggest that a common feature of ASC and PCO may be induction of an epithelial-mesenchymal transition by TGFβ.