INDUCTION OF CATARACT-LIKE CHANGES IN RAT LENS EPITHELIAL EXPLANTS BYTRANSFORMING GROWTH-FACTOR-BETA

Purpose. To investigate the possible role of transforming growth facto r beta (TGF(beta)) in lens development and growth, the authors studied the influence of TGF(beta), alone and in combination with fibroblast growth factor (FGF), on lens epithelial explants. Methods. Lens explan ts were prepared from both postnatal and adult rats, and changes durin g 5 days of culture with growth factor(s) were monitored by light and electron microscopy, immunolocalization of laminin, heparan sulfate pr oteoglycan and fiber-specific crystallins, and crystallin enzyme-linke d immunosorbent assays. Results. TGF(beta) induced cells in explants t o undergo an extensive and rapid elongation with features that disting uished it from FGF-induced fiber differentiation. TGF(beta) also induc ed accumulation of extracellular matrix, capsule wrinkling, cell death by apoptosis, and distinctive arrangements of cells. Standard explant s from 10-day-old rats responded to TGF(beta) only in the presence of FGF. Comparable explants from adult rats or from 21-day-old rats (cult ured on a laminin substratum) responded readily to TGF(beta) whether o r not FGF was present. Conclusions. First, these results suggest a rol e for TGF(beta) in regulating normal processes in lens cells such as t he production of extracellular matrix and capsule formation. Second, b ecause many of the changes induced by TGF(beta) resembled changes repo rted to occur during the formation of various kinds of subcapsular cat aracts, the results suggest that detailed studies of factors that infl uence the ability of lens cells to respond to TGF(beta) and the bioava ilability of TGF(beta) in the ocular media may provide important insig hts into the etiology of some forms of cataract.