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

Cooksley, Grace; Nam, Mi‐Hyun; Nahomi, Rooban B; Rankenberg, Johanna; Smith, Andrew JO; Wormstone, Yvette M; Wormstone, I Michael; (2024) Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts. Aging Cell , Article e14249. 10.1111/acel.14249. (In press). Green open access

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Abstract

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.

Type: Article
Title: Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/acel.14249
Publisher version: http://dx.doi.org/10.1111/acel.14249
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
Keywords: advanced glycation end products, epithelial-mesenchymal transition, lens epithelial cells, posterior capsule opacification, senescence
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10196872
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