Glutathione and catalase suppress TGFß-induced cataract-related changes in cultured rat lenses and lens epithelial explants

Purpose: The damaging effects of oxidative stress and transforming growth factor-β (TGFβ)-induced transdifferentiation of lens epithelial cells have both been implicated independently in the etiology of cataract. The aim of this study was to investigate whether the presence of antioxidant systems in the lens influences the ability of lens epithelial cells to respond to TGFβ. Methods: Whole lenses from young rats were cultured with or without TGFβ in the presence or absence of reduced glutathione (GSH). Lens epithelial explants from weanling rats were used to investigate the effects of GSH and catalase on TGFβ-induced cataract-related changes. Lenses were monitored for opacification for three to four days, photographed, and then processed for routine histology. Explants were assessed by phase contrast microscopy, enzyme-linked immunosorbent assay (ELISA) of α-smooth muscle actin (αSMA), and/or immunolocalization of αSMA and Pax6, markers for transdifferentiation and normal lens epithelial phenotype, respectively. Results: In cultured lenses, GSH strongly suppressed TGFβ-induced opacification and subcapsular plaque formation. In explants, both GSH and catalase suppressed changes typically associated with TGFβ-induced transdifferentiation including wrinkling of the lens capsule, cell-surface blebbing, apoptotic cell loss, induction of αSMA, and loss of Pax6 expression. Conclusions: This study suggests that antioxidant systems present in the normal lens, which protect the epithelium against the damaging effects of reactive oxygen species, may also serve to protect it against the potentially cataractogenic effects of TGFβ. Taken together with other recent studies, it also raises the possibility that TGFβ may induce cataract-related changes in lens epithelial cells via release of hydrogen peroxide.