Expression and role of integrins in lens development and cataractogenesis

The mammalian lens is composed of two types of cells enclosed within a thickened basement membrane known as the lens capsule. A monolayer of epithelial cells lines the anterior of the lens while the bulk of the lens is made up of lens fibre cells. After embryonic induction, the lens grows by the proliferation, posterior migration and differentiation of lens epithelial cells in the equatorial region into lens fibre cells. The central epithelium remains relatively quiescent. As fibre cells are formed, they are added to the fibre mass. Here they lose their nuclei and organelles and remain in the lens throughout life, moving filrther into the fibre mass as new cells are added cortically. Abnormal differentiation of lens cells into myofibroblastic/fibroblastic cell-types — an epithelial—mesenchymal transition — results in cataract (anterior subcapsular and posterior capsular opacification). This results in the formation of plaques containing these transformed cells, which express OL—smooth muscle actin, and aberrant matrix proteins, for example collagens I, III, IV, laminin, fibronectin and tenascin. This abnormal transformation can be induced both in vitro and in vivo by TGFB (transforming growth factor B). In lens epithelial explants and whole lens cultures, the addition of TGFB induces the transformation of epithelial cells into myofibroblastic/fibroblastic cell—types. The over-expression of TGFB in lenses of transgenic mice induces the formation of anterior subcapsular plaques which contain not only myofibroblastic/fibroblastic-type cells expressing a—smooth muscle actin, but also fibre-like cells expressing B-crystallin. Both normal and abnormal lens differentiation require dramatic changes in cell morphology, positioning and expression of molecular markers. This requires major changes in expression and activation state of cell adhesion molecules. The integrins are a major family of cells adhesion molecules that play a role in cell-cell and cell—matrix adhesion. They consist of an 0L and a [3 subunit that form a dimer on the plasma membrane and, when active, are linked to specific ligands externally and signalling molecules internally. The Bl group of integrins are mainly involved in cell-matrix adhesion and the mRNA expression of a3, a6 and [31 integrins in the lens was previously studied by this candidate. It was shOWn that the 0L3A subunit was exclusively expressed in the lens epithelium. The (x6B was also expressed in the epithelium and down-regulated in lens fibres while the 0L6A subunit was weakly expressed in the epithelium and up-regulated in lens fibres. The [31 was expressed in both lens epithelium and fibres.