Wound healing and epithelial-mesenchymal transition in the lens epithelium: Roles of growth factors and extracellular matrix

Abstract

The process of tissue fibrosis is characterized by the appearance of myofibroblasts, the key cell type involved in the fibrogenic reaction, and by the excess and disorganized accumulation of extracellular matrix, with resultant tissue contraction and impaired tissue function. Local inflammation is involved in this process with the supply of profibrogenic factors. This is also the case in posterior capsular opacification (PCO). In PCO, tissue myofibroblasts are generated from lens epithelial cells, the only cell lineage in the crystalline lens, through epithelial-mesenchymal transition (EMT), a process through which an epithelial cell changes its phenotype to become more like a mesenchymal cell, with the exception of fibroblast-derived myofibroblasts. Transforming growth factor β (TGFβ) is one of the major growth factors/cytokines involved in the process of EMT, although various other factors expressed by injured tissues orchestrate the EMT process. Among TGFβ signaling cascades, Smad signaling is considered to play a critical role, although other classical mitogen-activated protein kinases also have important roles in modulating lens EMT. The lens epithelium also has the ability to form other types of PCO, regenerated lentoid structures of Soemmering's rings and Elschnig's pearls, both containing crystalline lens-like components. PCO tissue is also characterized by the accumulation of EMT-lens cell-derived matricellular components, i.e., tenascin C, osteopontin, and lumican, that further modulate Smad signaling and EMT of these cells. Fibroblast growth factor reportedly also plays an important role in lens tissue regeneration. PCO-related signal transduction cascades, such as Smad signaling, could be a putative target for the prevention or treatment of unfavorable PCO.