Differential cataractogenic potency of tgf-β₁, β₂, and -β₃ and their expression in the postnatal rat eye

Purpose. Tranforming growth factor-β has been shown to induce cataractous changes in rat lenses. This study assesses the relative cataractogenic potential of TGF-β₁, TGF-β₂, and TGF-β and their expression patterns in the rat eye. Methods. Lens epithelial explants and whole lenses from weanling rats were cultured with TFG-β₁, TGF-β₂, or TGF-β₃ at concentrations ranging from 0.025 ng/ml to 4 ng/ml for 3 to 5 days. Cataractous changes were monitored daily by phase contrast microscopy and by immunofluorescent detection of cataract markers α-smooth muscle actin and type I collagen. Expression of TGF-β was studied by immunofluorescence and in situ hybridization on eye sections from neonatal and weanling rats. Results. All three isoforms induced morphologic changes in lens epithelial explants and cultured lenses that are typically associated with human subcapsular cataract. Transforming growth factor-β₂ and TGF-β₃ were approximately 10 times more potent than TGF-β₁. All there isoforms were expressed in the eye in spatially distinct but overlapping patterns. Transforming growth factor-β₁ and TGF-β₂ and their mRNA were detected in most ocular tissues, including the lens. Although TGF-β₃ was immunolocalized in lens epithelium and fibers and in other ocular tissues, its mRNA was detected only in the retina and choroid. Conclusions. All three isoforms of TGF-β are potentially available to lens cells and have the potential to induce cataractous changes. The results suggest that TGF-β activity is normally tightly regulated in the eye. Activation of TGF-β in the lens environment, such as may occur during injury, in wound healing, or in pathologic conditions may contribute to cataractogenesis in vivo.