Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts

• Published in: Aging cell Vol. 23; no. 10; pp. e14249 - n/a
• Main Authors: Cooksley, Grace, Nam, Mi‐Hyun, Nahomi, Rooban B., Rankenberg, Johanna, Smith, Andrew J. O., Wormstone, Yvette M., Wormstone, I. Michael, Nagaraj, Ram H.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2024; John Wiley and Sons Inc
• Subjects: advanced glycation end products; Advanced glycosylation end products; Age; Aged; Aging; Cataract - metabolism; Cataract - pathology; Cataracts; Cell culture; Cell cycle; Cells, Cultured; Cellular Senescence - drug effects; Cyclin-dependent kinases; Edema; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; epithelial‐mesenchymal transition; Extracellular matrix; Eye lens; Eye surgery; Fibrosis; Genotype & phenotype; Glycation End Products, Advanced - metabolism; Growth factors; Humans; Intraocular lenses; Kinases; Lens Capsule, Crystalline - metabolism; Lens Capsule, Crystalline - pathology; lens epithelial cells; posterior capsule opacification; Proteins; Reactive oxygen species; Senescence; Smooth muscle; Surgery; senescence; posterior capsule opacification; advanced glycation end products; epithelial‐mesenchymal transition; lens epithelial cells
• ISSN: 1474-9718; 1474-9726; 1474-9726
• DOI: 10.1111/acel.14249

Posterior capsule opacification (PCO) is a common complication after cataract surgery. Residual lens epithelial cells (LECs) on the anterior lens capsule, after cataract surgery, migrate to the posterior lens capsule and undergo transdifferentiation into myofibroblast‐like cells. Those cells synthesize excessive amounts of extracellular matrix and contribute to fibrosis during PCO. Cellular senescence, a phenomenon that increases with aging, has been implicated in several fibrotic diseases. Here, we have investigated the prevalence of senescent LECs within the lens posterior capsule and the ability of advanced glycation end products (AGEs) in lens capsules to induce senescence, contributing to PCO. Aged lens capsules from pseudophakic human cadaver eyes showed the presence of senescent LECs. In human capsular bags, LECs showed an age‐dependent increase in senescence after 28 days of culture. Human LECs cultured on aged lens capsules for 3 days underwent senescence; this effect was not seen in LECs cultured on young lens capsules. Human LECs cultured on an AGE‐modified extracellular matrix (ECM‐AGEs) showed an AGE‐concentration‐dependent increase in the expression of senescence markers and reactive oxygen species (ROS) levels. Treatment with a RAGE antagonist and ROS inhibitor reduced the expression of senescence and fibrotic markers. Additionally, conditioned media from ECM‐AGEs‐treated cells induced the expression of fibrotic markers in naïve LECs. Together, these suggest that AGEs in the capsule induce senescence of LECs, which triggers the mesenchymal transition of neighboring non‐senescent LECs and contributes to PCO. Advanced glycation end products (AGEs) in the posterior capsule of the lens induce senescence of lens epithelial cells (LECs). The senescent LECs secrete senescence‐associated secretory phenotype (SASP) and promote epithelial‐to‐mesenchymal transition of non‐senescent LECs. These events could potentially contribute to fibrosis during the development of posterior capsule opacification after cataract surgery in elderly patients.