Consecutive dosing of UVB irradiation induces loss of ABCB5 expression and activation of EMT and fibrosis proteins in limbal epithelial cells similar to pterygium epithelium

M. Domdey; M.A. Kluth; C. Maßlo; C. Ganss; M.H. Frank; N.Y. Frank; M.T. Coroneo; C. Cursiefen; M. Notara

Stem Cell Research (Oct 2022)

Consecutive dosing of UVB irradiation induces loss of ABCB5 expression and activation of EMT and fibrosis proteins in limbal epithelial cells similar to pterygium epithelium

M. Domdey,
M.A. Kluth,
C. Maßlo,
C. Ganss,
M.H. Frank,
N.Y. Frank,
M.T. Coroneo,
C. Cursiefen,
M. Notara

Affiliations

M. Domdey: Dept. of Ophthalmology, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany
M.A. Kluth: TICEBA GmbH, Im Neuenheimer Feld 517, Heidelberg, Germany; RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, Heidelberg, Germany
C. Maßlo: TICEBA GmbH, Im Neuenheimer Feld 517, Heidelberg, Germany; RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, Heidelberg, Germany
C. Ganss: TICEBA GmbH, Im Neuenheimer Feld 517, Heidelberg, Germany; RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, Heidelberg, Germany
M.H. Frank: Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia
N.Y. Frank: Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Department of Medicine, VA Boston Healthcare System, Boston, MA, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA
M.T. Coroneo: Department of Ophthalmology, University of New South Wales, Prince of Wales Hospital, Sydney, Australia; Ophthalmic Surgeons, Sydney, Australia; East Sydney Private Hospital, Sydney, Australia; Look for Life Foundation, Sydney, Australia
C. Cursiefen: Dept. of Ophthalmology, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany; Institute for Genome Stability in Ageing and Disease, CECAD Research Center, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMK), University of Cologne, Germany
M. Notara: Dept. of Ophthalmology, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany; Institute for Genome Stability in Ageing and Disease, CECAD Research Center, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMK), University of Cologne, Germany; Corresponding author at: Dept. of Ophthalmology, University of Cologne, Kerpener Straße 62, 50937 Cologne, Germany.

Journal volume & issue: Vol. 64
p. 102936

Abstract

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Pterygium pathogenesis is often attributed to a population of altered limbal stem cells, which initiate corneal invasion and drive the hyperproliferation and fibrosis associated with the disease. These cells are thought to undergo epithelial to mesenchymal transition (EMT) and to contribute to subepithelial stromal fibrosis. In this study, the presence of the novel limbal stem cell marker ABCB5 in clusters of basal epithelial pterygium cells co-expressing with P63α and P40 is reported. ABCB5-positive pterygium cells also express EMT-associated fibrosis markers including vimentin and α-SMA while their β-catenin expression is reduced. By using a novel in vitro model of two-dose UV-induced EMT activation on limbal epithelial cells, we could observe the dysregulation of EMT-related proteins including an increase of vimentin and α-SMA as well as downregulation of β-catenin in epithelial cells correlating to downregulation of ABCB5. The sequential irradiation of limbal fibroblasts also induced an increase in vimentin and α-SMA. Taken together, these data demonstrate for the first time the expression of ABCB5 in pterygium stem cell activity and EMT-related events while the involvement of limbal stem cells in pterygium pathogenesis is exhibited via sequential irradiation of limbal epithelial cells. The later in vitro approach can be used to further study the involvement of limbal epithelium UV-induced EMT in pterygium pathogenesis and help identify novel treatments against pterygium growth and recurrence.

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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