TGFβ Receptor Expression in Lens: Implications for Differentiation and Cataractogenesis

TGFβ induces changes characteristic of some forms of cataract. However, the responsiveness of lens epithelial cells to TGFβ is age-dependent; weanling and adult, but not neonatal, lens epithelial cells respond. This study investigated TGFβ receptor (TβRI and TβRII) expression during rat lens development and the effects of FGF-2 on TGFβ responsiveness and TβR expression. Immunofluorescence, immunoblotting, RT-PCR and in situ hybridization were used to examine the spatio-temporal expression patterns of TβR. Lens explants were used to investigate the effects of FGF-2 on TGFβ responsiveness and TβR expression. In the lens epithelium, little or no immunoreactivity was detected at P3 but at P21 there was distinct reactivity for TβRI and TβRII. 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 TβRI (30, 50, 90kDa) and TβRII (70–120kDa). In situ hybridization with a rat probe for Alk5 (TβRI) showed that the lens expresses Alk5 mRNA in epithelium and fibers throughout development. A rat TβRII probe revealed distinct expression of a TβRII 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 TGFβ but P13 explants did. Addition of FGF-2 to P9 explants induced increased TβR immunoreactivity and enhanced the competency of lens epithelial cells to respond to TGFβ. These data indicate that the overall increased expression of TGFβ receptors in lens epithelium during postnatal development (P3–P21) underlies an age-related change in TGFβ responsiveness. The results also suggest that lens cells may express multiple forms of TβR. Expression of TβR in lens fibers throughout lens development and the induction of enhanced TβR expression by FGF suggest a role for TGFβ signaling during FGF-induced responses and fiber differentiation.