Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification

Abstract

Posterior capsule opacification (PCO) is a frequent complication after cataract surgery, and advanced PCO requires YAG laser (Nd: YAG) capsulotomy, which often gives rise to more complications. Lens epithelial cell (LEC) proliferation and transformation (i.e., epithelial–mesenchymal transition (EMT)) are two critical elements in PCO initiation and progression pathogenesis. While PCO marginally impacts aged cataract surgery patients, PCO incidences are exceptionally high in infants and children undergoing cataract surgery. The gene expression of lens epithelial cell aging and its role in the discrepancy of PCO prevalence between young and older people have not been fully studied. Here, we conducted a comprehensive differentially expressed gene (DEG) analysis of a cell aging model by comparing the early and late passage FHL124 lens epithelial cells (LECs). In vitro, TGFβ2, cell treatment, and in vivo mouse cataract surgical models were used to validate our findings. We found that aged LECs decelerated rates of cell proliferation accompanied by dysregulation of cellular immune response and cell stress response. Surprisingly, we found that LECs systematically downregulated epithelial–mesenchymal transition (EMT)-promoting genes. The protein expression of several EMT hallmark genes, e.g., fibronectin, αSMA, and cadherin 11, were gradually decreased during LECs aging. We then confirmed these findings in vitro and found that aged LECs markedly alleviated TGFβ2-mediated EMT. Importantly, we explicitly confirmed the in vitro findings from the in vivo mouse cataract surgery studies. We propose that both the high proliferation rate and EMT-enriched young LECs phenotypic characteristics contribute to unusually high PCO incidence in infants and children.

Lens epithelial cell response to polymer stiffness and polymer chemistry

“…This could be due to the stiffness of T:H 1:1, as hLECs may spread more on stiffer surfaces, a behavior which has been demonstrated in other cell types 29,31,34 . This change in cell phenotype could be an indication of EMT, 35 which is a known phenotypic change associated with PCO 7,36 . The pHEMA samples had lower stiffness than T:H 1:1, and its AR was also significantly lower than T:H 1:1 ( p < 0.01).…”

“…29,31,34 This change in cell phenotype could be an indication of EMT, 35 which is a known phenotypic change associated with PCO. 7,36 The pHEMA samples had lower stiffness than T:H 1:1, and its AR was also significantly lower than T:H 1:1 ( p < 0.01).…”

“…[4][5][6] During PCO formation, residual LECs aberrantly migrate to the posterior capsule, undergo epithelialmesenchymal transition (EMT), and become fibrotic resulting in secondary vision loss. 7 Although PCO can be treated with neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy, the procedure is costly and has increased risk of side effects including damage to the IOL, increase in intraocular pressure, posterior vitreous detachment, and retinal breaks or detachment. [8][9][10][11] Moreover, Nd:YAG is difficult to perform in pediatric patients.…”

Long Non-Coding RNA H19 Prevents Lens Fibrosis through Maintaining Lens Epithelial Cell Phenotypes

“…Many studies have been conducted to explore the potential therapeutic options for preventing or reversing lens fibrosis using diverse experimental models. To better validate their roles in lens transparency maintenance, in recent years, apart from in vitro studies using lens epithelial cell lines, semi-in vivo epithelial explants, the whole lens culturing, and in vivo animal models have been more widely used, including injury-induced ASC models, mock lens cataract surgery (Extracapsular Lens Extraction, ECLE) for PCO models, and transgenic/genetic knockout mice [ 19 , 52 , 53 , 54 , 55 , 56 , 57 ]. It is generally accepted that during TGF-β2-induced EMT, loss of LEC integrity is accompanied by the abnormal secretion of ECM and aberrant cell migration, resulting in fibrotic plaques and lens opacification.…”

Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation

“…In addition, cataract surgery can lead to complications such as posterior capsule opacification (PCO), also known as secondary cataract, which is the most common complication following cataract surgery. Severe PCO may require further surgery, such as a Yttrium aluminum garnet (YAG) laser capsulotomy, which can introduce additional complications, such as increasing transient intraocular pressure, lens subluxation and dislocation, retinal detachment and lens pitting, exacerbation of local endophthalmitis, and free-floating fragments (4)(5)(6)(7).…”