AGEs in human lens capsule promote the TGF2-mediated EMT of lens epithelial cells: implications for age-associated fibrosis

Proteins in basement membrane (BM) are long-lived and accumulate chemical modifications during aging; advanced glycation endproduct (AGE) formation is one such modification. The human lens capsule is a BM secreted by lens epithelial cells. In this study, we have investigated the effect of aging and cataracts on the AGE levels in the human lens capsule and determined their role in the epithelial-to-mesenchymal transition (EMT) of lens epithelial cells. EMT occurs during posterior capsule opacification (PCO), also known as secondary cataract formation. We found age-dependent increases in several AGEs and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC-MS/MS. The TGF beta 2-mediated upregulation of the mRNA levels (by qPCR) of EMT-associated proteins was significantly enhanced in cells cultured on AGE-modified BM and human lens capsule compared with those on unmodified proteins. Such responses were also observed for TGF beta 1. In the human capsular bag model of PCO, the AGE content of the capsule proteins was correlated with the synthesis of TGF beta 2-mediated alpha-smooth muscle actin (alpha SMA). Taken together, our data imply that AGEs in the lens capsule promote the TGF beta 2-mediated fibrosis of lens epithelial cells during PCO and suggest that AGEs in BMs could have a broader role in aging and diabetes-associated fibrosis.