{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T04:56:34Z","timestamp":1777179394718,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Research Board Ireland","award":["HRB POA 2010-129"],"award-info":[{"award-number":["HRB POA 2010-129"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Optic nerve head (ONH) cupping is a clinical feature of glaucoma associated with extracellular matrix (ECM) remodelling and lamina cribrosa (LC) fibrosis. Peripapillary atrophy (PPA) occurs commonly in glaucoma, and is characterised by the loss of retinal pigment epithelium (RPE) adjacent to the ONH. Under pro-fibrotic conditions, epithelial cells throughout the body can differentiate into fibroblast-like cells through epithelial-to-mesenchymal transition (EMT) and contribute to ECM fibrosis. This is investigated here in the context of glaucoma and PPA. Human-donor ONH sections were assessed for the presence of the RPE cell-specific marker RPE65 using immunofluorescence. We examined the EMT response of ARPE-19 cells to the following glaucoma-related stimuli: cyclic mechanical stretch, mechanical stiffness, transforming growth factor beta (TGF\u03b2), and tumour necrosis factor alpha (TNF\u03b1). The gene expression was measured using the PCR of the epithelial tight junction marker zona occludens 1 (ZO-1) and the mesenchymal markers alpha smooth muscle actin (\u03b1SMA) and vimentin. A scratch assay was used to assess the ARPE-19 migration. Significant RPE-65 staining was demonstrated in the glaucomatous ONH. The cyclic stretching and substrate stiffness of the ARPE-19 cells caused a significant decrease in ZO-1 (p = 0.04), and an increase in \u03b1SMA (p = 0.04). The scratch assays demonstrated increased migration of ARPE19 in the presence of TNF\u03b1 (p = 0.02). Furthermore, ARPE-19 cells undergo an EMT-like transition (gain of \u03b1SMA, loss of ZO-1 and increased migration) in response to glaucomatous stimuli. This suggests that during PPA, RPE cells have the potential to migrate into the ONH and differentiate into fibroblast-like cells, contributing to glaucomatous ONH cupping.<\/jats:p>","DOI":"10.3390\/jcm12072737","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T05:54:39Z","timestamp":1680760479000},"page":"2737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of Epithelial-to-Mesenchymal Transition of Retinal Pigment Epithelial Cells in Glaucoma Cupping"],"prefix":"10.3390","volume":"12","author":[{"given":"Eabha","family":"O\u2019Driscoll","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustapha","family":"Irnaten","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3940-198X","authenticated-orcid":false,"given":"Markus","family":"Kuehn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA 52240, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Wallace","sequence":"additional","affiliation":[{"name":"School of Medicine, University College Dublin, D04V1W8 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colm","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland"},{"name":"School of Medicine, University College Dublin, D04V1W8 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/bjo.77.2.103","article-title":"Direct clinico-histological correlation of parapapillary chorioretinal atrophy","volume":"77","author":"Kubota","year":"1993","journal-title":"Br. 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