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

Autor: Cooksley G; Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, Colorado, USA., Nam MH; Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, Colorado, USA., Nahomi RB; Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, Colorado, USA., Rankenberg J; Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, Colorado, USA., Smith AJO; School of Biological Sciences, University of East Anglia, Norwich, UK., Wormstone YM; School of Biological Sciences, University of East Anglia, Norwich, UK., Wormstone IM; School of Biological Sciences, University of East Anglia, Norwich, UK.; Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, China., Nagaraj RH; Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, Colorado, USA.; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Oct; Vol. 23 (10), pp. e14249. Date of Electronic Publication: 2024 Jun 21.
DOI: 10.1111/acel.14249
Abstrakt: 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.
(© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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