Tgfβ-Smad signalling in postoperative human lens epithelial cells

Abstract

Aims: To localise Smads3/4 proteins in lens epithelial cells (LECs) of fresh and postoperative human specimens. Smads3/4 are involved in signal transduction between transforming growth factor β (TGFβ) cell surface receptors and gene promoters. Nuclear localisation of Smads indicates achievement of endogenous TGFβ signalling in cells. Methods: Three circular sections of the anterior capsule, one lens, and 17 capsules undergoing postoperative healing were studied. Immunohistochemistry was performed for Smads3/4 in paraffin sections of the specimens. The effect of exogenous TGFβ2 on Smad3 subcellular localisation was examined in explant cultures of extracted human anterior lens epithelium. Results: The cytoplasm, but not the nuclei, of LECs of uninjured lenses was immunoreactive for Smads3/4. In contrast, nuclear immunoreactivity for Smads3/4 was detected in LECs during capsular healing. Nuclei positive for Smads3/4 were observed in monolayered LECs adjacent to the regenerated lens fibres of Sommerring's ring. Interestingly, the nuclei of LECs that were somewhat elongated, and appeared to be differentiating into fibre-like cells, were negative for Smads3/4. Fibroblast-like, spindle-shaped lens cells with nuclear immunoreactivity for nuclear Smads3/4 were occasionally observed in the extracellular matrix accumulated in capsular opacification. Exogenous TGFβ induced nuclear translocation of Smad3 in LECs of anterior capsule specimens in explant culture. Conclusions: This is consistent with TGFβ induced Smad signalling being involved in regulating the behaviour of LECs during wound healing after cataract surgery.