The Lens Capsule: Synthesis, Remodeling, and MMPs

The lens capsule is an amorphous, elastic structure that encapsulates the ocular lens. It is secreted by cells of the lens and is composed primarily of type IV collagen and laminin along with additional extracellular matrix (ECM) components such as entactin/nidogen, heparin sulfate proteoglycans (HSPG), and secreted protein acidic and rich in cysteine (SPARC), which act to stabilize the lens capsule structure. As the lens grows during development and with age, new capsular lamellae are synthesized, deposited, and organized by the lens epithelial and fiber cells. The main receptors of lens cells that adhere them to the ECM of the capsule are the integrins, heterodimeric transmembrane cell adhesion molecules. These adhesion molecules also act as bidirectional signaling molecules, mediating signals between the lens and the surrounding ocular media. The composition and arrangement of both the ECM of the lens capsule and the integrins are altered in fibrotic cataracts such as posterior capsule opacification (PCO) and anterior subcapsular cataract (ASC). This includes the aberrant deposition of ECM components not normally expressed in the lens capsule and a corresponding change in the profile of integrins expressed in the lens. The matrix metalloproteinases (MMPs), a family of matrix-degrading enzymes, have been shown to release growth factors from the lens capsule and activate receptors. They are also aberrantly expressed in PCO and ASC and their inhibition has been shown to suppress events involved in fibrotic cataract formation including lens epithelial cell migration, capsular contraction, and the transformation of cells into myofibroblasts.