Abstract
The migration of lens epithelial cells towards the posterior capsule is a key event in the development of posterior capsule opacification (PCO). Accumulating evidence has described crosstalk between growth factors and adhesive signaling pathways in wound healing and cell migration. The aim of the present study was to elucidate an aberrant transforming growth factor (TGF)‑β2 signaling pathway that regulated the migration of lens epithelial cells in the pathological context of PCO. The expression of fibronectin, focal adhesion kinase (FAK) and phosphorylated (p)‑FAK in HLE‑B3 cells following TGF‑β2 treatment was determined by western blot analysis and the expression of integrin α5β1 was detected by flow cytometry. Cell migration capacity was measured by wound healing and Transwell assays in the presence of 1,2,4,5‑tetraaminobenzene tetrahydrochloride, a selective FAK inhibitor, fibronectin small interfering RNA interference, arginylglycylaspartic acid peptides or α5β1‑integrin neutralizing antibodies. The 1,2,4,5‑tetraaminobenzene tetrahydrochloride was administered daily to 16 rabbits following cataract surgery. Fibronectin and TGF‑β expression were increased in the PCO group, demonstrated by immunofluorescence assays. PCO grading was conducted by slit‑lamp biomicroscopy and evaluation of posterior capsule opacification software. It was observed that TGF‑β2 promoted HLE‑B3 cell migration and upregulated fibronectin expression, which was followed by an increased phosphorylation of FAK. In addition, TGF‑β2 treatment and fibronectin surface coating significantly increased cell migration and FAK activation, which was inhibited by disrupting fibronectin‑integrin α5β1 interaction with the arginylglycylaspartic acid peptide, α5β1‑integrin neutralizing antibody or fibronectin depletion. Finally, suppression of FAK signaling by its inhibitor significantly decreased cell migration in vitro and attenuated PCO development in vivo. In summary, TGF‑β2 was indicated to promote the migration of lens epithelial cells through the TGF‑β2/fibronectin/integrin/FAK axis. Inhibition of FAK activity decreased TGF‑β2‑mediated cell migration in vitro and improved the symptoms of PCO in a rabbit model.