Cataract induction in lenses cultured with transforming growth factor-β

Purpose. Anterior subcapsular cataracts are characterized by the appearance of opaque plaques of abnormal cells. Distinctive spindle-shaped cells containing α-smooth muscle actin are present and are associated with wrinkling of the overlying lens capsule. Accumulations of extracellular matrix, including type I collagen, also are found. The authors previously reported that transforming growth factor-β (TGF-β) induces similar aberrant morphologic changes in lens epithelial explants. More recently, they identified α-smooth muscle actin in explants cultured with TGF-β. The aim of this study was to determine whether TGF-β induces comparable cataractous changes in whole lenses and to examine the effects of this treatment on the transparency of the lens. Methods. Whole lenses from 21-day-old rats were cultured in defined serum-free medium with TGF-β2 or without added growth factors for 5 days. Lenses were then photographed and prepared for histology and immunolocalization. Results. Lenses cultured with TGF-β developed distinct anterior opacities just beneath the lens capsule. Histologically, clumps of abnormal cells corresponded with these opacities. Spindle-shaped cells, which contained α-smooth muscle actin, were present, and the overlying capsule was often wrinkled. The clumps contained accumulations of type I collagen, laminin, and heparan sulphate proteoglycan. In contrast, lenses cultured without growth factors remained transparent, retained normal lens morphology, and did not accumulate α-smooth muscle actin or type I collagen. Conclusions. These results show that TGF-β induces whole lenses to form opacities that contain morphologic and biochemical markers for subcapsular cataract.