Induction of cataract-like changes in rat lens epithelial explants by transforming growth factor β

Purpose. To investigate the possible role of transforming growth factor β (TGF_β) in lens development and growth, the authors studied the influence of TGF_β, alone and in combination with fibroblast growth factor (FGF), on lens epithelial explants. Methods. Lens explants were prepared from both postnatal and adult rats, and changes during 5 days of culture with growth factor(s) were monitored by light and electron microscopy, immunolocalization of laminin, heparan sulfate proteoglycan and fiber-specific crystallins, and crystallin enzyme-linked immunosorbent assays. Results. TGF_β induced cells in explants to undergo an extensive and rapid elongation with features that distinguished it from FGF-induced fiber differentiation. TGF_β also induced accumulation of extracellular matrix, capsule wrinkling, cell death by apoptosis, and distinctive arrangements of cells. Standard explants from 10- day-old rats responded to TGF_β only in the presence of FGF. Comparable explants from adult rats or from 21-day-old rats (cultured on a laminin substratum) responded readily to TGF_β whether or not FGF was present. Conclusions. First, these results suggest a role for TGF_β in regulating normal processes in lens cells such as the production of extracellular matrix and capsule formation. Second, because many of the changes induced by TGF_β resembled changes reported to occur during the formation of various kinds of subcapsular cataracts, the results suggest that detailed studies of factors that influence the ability of lens cells to respond to TGF_β and the bioavailability of TGF_β in the ocular media may provide important insights into the etiology of some forms of cataract.