TGFβ receptor expression in lens:: Implications for differentiation and cataractogenesis

TGF beta induces changes characteristic of some forms of cataract. However, the responsiveness of lens epithelial cells to TGF beta is age-dependent; weanling and adult, but not neonatal, lens epithelial cells respond. This study investigated TGF beta receptor (T beta RI and T beta RII) expression during rat lens development and the effects of FGF-2 on TGF beta responsiveness and T betaR expression. Immunofluorescence, immunoblotting, RT-PCR and in situ hybridization were used to examine the spatio-temporal expression patterns of T betaR. Lens explants were used to investigate the effects of FGF-2 on TGF beta responsiveness and T betaR expression. In the lens epithelium, little or no immunoreactivity was detected at P3 but at P21 there was distinct reactivity for T beta RI and T beta RII. Reactivity for both receptors was also found in the differentiating fibers in the transitional zone and cortex at both ages. Western blotting of lens membrane extracts identified multiple molecular weight forms of T beta RI (30, 50, 90 kDa) and T beta RII (70-120 kDa). In situ hybridization with a rat probe for Alk5 (T beta RI) showed that the lens expresses Alk5 mRNA in epithelium and fibers throughout development. A rat T beta RII probe revealed distinct expression of a T beta RII mRNA in lens fibers throughout development and in the lens epithelium at P21 but not at P3. In vitro studies showed that lens epithelial explants from P9 rats did not undergo cataractous changes in response to TGF beta but P13 explants did. Addition of FGF-2 to P9 explants induced increased TPR immunoreactivity and enhanced the competency of lens epithelial cells to respond to TGF beta. These data indicate that the overall increased expression of TGF beta receptors in lens epithelium during postnatal development (P3-P21) underlies an age-related change in TGF beta responsiveness. The results also suggest that lens cells may express multiple forms of TPR. Expression of T betaR in lens fibers throughout lens development and the induction of enhanced T betaR expression by FGF suggest a role for TGF beta signaling during FGF-induced responses and fiber differentiation. (C) 2001 Academic Press.