Fibronectin regulates growth factor signaling and cell differentiation in primary lens cells

Lens epithelial cells are bound to the lens extracellular matrix capsule, a major component of which is laminin. After cataract surgery, surviving lens epithelial cells are exposed to increased levels of fibronectin. We asked if fibronectin influences lens cell fate using a serum-free primary lens epithelial cell culture system (DCDMLs). We found that culturing DCDMLs with plasma-derived fibronectin upregulated canonical TGFβ signaling relative to cells plated on laminin. Fibronectin-exposed cultures also showed increased, TGFβ signaling-dependent differentiation into the two cell types responsible for posterior capsule opacification after cataract surgery, namely myofibroblasts and lens fiber cells. Increased TGFβ activity could be recovered from the conditioned medium of cells grown on fibronectin. Other experiments showed that plating DCDMLs on fibronectin overcomes the need for BMP in FGF-induced lens fiber cell differentiation, a requirement that is restored when endogenous TGFβ signaling is inhibited. These results demonstrate how the TGFβ/fibronectin axis can profoundly affect lens cell fate. This axis represents a novel target for prevention of late-onset posterior capsule opacification, a common but currently intractable complication of cataract surgery.