Understanding Fibrotic Cataract: Regulation of TGFβ-Mediated Pathways Leading to Lens Epithelial to Mesenchymal Transition (EMT)

抄録

Different forms of human cataract, such as anterior subcapsular cataract (ASC) and posterior capsular opacification (PCO) result from an epithelial to mesenchymal transition (EMT) of lens epithelial cells. This key pathological mechanism is thought to be primarily driven by Transforming growth factor-beta (TGFß) , not only in cataract, but in many other fibrotic pathologies. Stimulation of cells by TGFß leading to EMT and subsequent cataract is regulated intracellularly by different signalling pathways including the canonical Smad, and non-canonical MAPK (ERK, p38) pathways. These pathways are thought to potentially crosstalk and together lead to a number of different EMT features, including loss of epithelial phenotype, myofibroblast cell differentiation, extracellular matrix (ECM) accumulation and even aberrant redox signalling. Earlier studies have shown that these TGFß-mediated pathways can be regulated by many different means such as by other growth factors (FGF, EGF, BMPs) , ECM proteins and modulators, and intracellular molecules such as members of the Sprouty family, that in turn negatively regulate the Smad- and MAPK-signaling pathways. Here we review our current work examining the different modes of regulating the molecular mechanisms that drive EMT in the lens. We hope that with a better understanding of these processes, this will lead to more effective means of controlling this lens pathology and subsequently lead to the development of novel non-invasive therapeutics for human cataract.