Cell Adhesion Molecule Expression in Human Lens Epithelial Cells After Corticosteroid Exposure

Celojevic, Dragana; Carlsson, Therese; Br, Johansson; Nannmark, Ulf; Petersen, Anne

doi:10.2174/1874364101206010042

Cited by 10 publications

(8 citation statements)

References 35 publications

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“…Expression of lens adhesion molecules N-cadherin, α-catenin, β-catenin and GR was significantly decreased in dexamethasone exposed lens cells with suspected to contribute to contribute to the pathogenesis of posterior subcapsular opacification [45].…”

Section: Discussionmentioning

confidence: 97%

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

El‐Sayyad¹,

Ym²,

Khalifa³

et al. 2017

J Mol Biomark Diagn

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Section: Discussionmentioning

confidence: 97%

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

El‐Sayyad¹,

Ym²,

Khalifa³

et al. 2017

J Mol Biomark Diagn

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“…This characteristic of native LECs has been previously reported. [ 28 29 ] FHL124 cells, generated from human capsular epithelial explants, have 99.5% homology with native human LECs. [ 30 ]…”

Section: Discussionmentioning

confidence: 99%

Trichostatin a restores expression of adherens and tight junction proteins during transforming growth factor β-Mediated epithelial-to-mesenchymal transition

Ganatra¹,

Vasavada²,

Vidya³

et al. 2018

J Ophthalmic Vis Res

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Purpose:Adherens junctions and polarity markers play an important role in maintaining epithelial phenotype but get altered during the epithelial-mesenchymal transition (EMT). Alterations of these markers during EMT of lens epithelial cell (LEC) can lead to vision compromising conditions. The aim of this study was to examine if Trichostatin-A (TSA), a histone deacetylase inhibitor, can prevent EMT by restoring the adherens junction complex in LEC.Methods:Fetal human lens epithelial cell line (FHL124) was used. Cells were treated with 10 ng/ml TGF-β2 in the presence or absence of TSA. Real time-PCR and western blotting were carried out for HDAC1, HDAC2, CDH1 (E-cad), TJP1 (ZO-1) and CTNNB1 (β-cat). Level of histone acetylation was analyzed by western blotting. Chromatin Immunoprecipitation was carried out to study the level of acetylated histone H4 and HDAC2 at the promoter regions of CDH1, TJP1, and CTNNB1. E-cad, ZO-1, and β-cat were localized using immunofluorescence. Kruskal-Wallis test was used for statistical analysis.Results:TSA down-regulated HDAC1 and HDAC2 and led to an increase in global acetylation. The mRNA and protein levels of E-cad, ZO-1, and β-cat decreased during EMT but were up-regulated by TSA treatment. TSA also helped in stabilizing these proteins at cell-cell junctions during EMT. TSA decreases association of HDAC2 at the promoter regions of adherens junction genes while increasing histone H4 acetylation status.Conclusion:TSA increases histone acetylation and restores the adherens junction complex in LECs. TSA helps in preventing EMT and thus shows potential against lens fibrosis and vision compromising conditions.

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“…The absence of E-cadherin was confirmed using different primer probes. Celojevic et al 29 were also not able to detect E-cadherin expression by immunohistochemistry and by western blot in human lens epithelial cells derived from cataract surgery in patients. On the contrary, Fu et al 10 were able to detect E-cadherin in lentoid bodies made from humaninduced pluripotent stem cells derived from urinary cells.…”

Section: Spheroids Made From Human Lens Epithelial Cells Are Rapidly mentioning

confidence: 93%

A Human Three-Dimensional In Vitro Model of Lens Epithelial Cells as a Model to Study Mechanisms of Drug-Induced Posterior Subcapsular Cataracts

Plüss

Kustermann

2020

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Cataract is a pathological opacification of the lens, which is still one of the leading causes of blindness in the world. Several etiologies are described, among them drug-induced cataract, for example, posterior subcapsular cataract (PSC) after steroid treatment. To investigate different mechanisms of drug-induced cataract a human three-dimensional (3D) lens in vitro model was developed, consisting of immortalized human lens epithelial cells. Methods: These cells were cultivated on 96-well, ultralow attachment plates, where they rapidly form spheroids. By gene expression analysis different markers were observed, which are important to maintain lens transparency, such as ephrin type-A receptor 2 (EphA2) or a-smooth muscle actin (a-SMA). Results: The lens epithelial cells form a spheroid within a few days and show stable expression of important lens marker, and size and viability remain stable up to 26 days in culture. The gene expression of the glucocorticoid-treated spheroids revealed a clear shift in the expression of EphA2, a-SMA, aB-crystallin (CRYAB), and heat shock protein beta-1 (HSPB1). Furthermore, the glucocorticoid treatment did not improve cell survival. Conclusions: This study proposes a useful 3D in vitro model, which expresses important lens markers and is capable of demonstrating features found in drug-induced cataracts. As the viability remains stable over long time, this model can also be used for long-term treatment. The main characteristics are the increased expression of a-SMA, CRYAB, and HSPB1 and the decreased expression of EphA2. The present data provide some first evidence on novel mechanisms involved in glucocorticoid-induced cataracts.

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Cell Adhesion Molecule Expression in Human Lens Epithelial Cells After Corticosteroid Exposure

Cited by 10 publications

References 35 publications

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

Trichostatin a restores expression of adherens and tight junction proteins during transforming growth factor β-Mediated epithelial-to-mesenchymal transition

A Human Three-Dimensional In Vitro Model of Lens Epithelial Cells as a Model to Study Mechanisms of Drug-Induced Posterior Subcapsular Cataracts

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