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.

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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christoph Ganss reports financial support was provided by Ticeba GmbH. Markus H Frank reports financial support was provided by Ticeba GmbH. Maria Notara reports equipment, drugs, or supplies was provided by Ticeba GmbH. Christoph Masslo reports financial support was provided by Ticeba GmbH. Andreas Kluth reports financial support was provided by Ticeba GmbH. Christoph Ganss reports a relationship with Ticeba GmbH that includes: board membership. Andreas Kluth reports a relationship with Ticeba GmbH that includes: employment. Christoph Masslo reports a relationship with Ticeba GmbH that includes: employment. Markus Frank reports a relationship with Ticeba GmbH that includes: consulting or advisory. Maria Notara reports a relationship with Ticeba GmbH that includes: non-financial support. Markus Frank has patent issued to Ticeba Gmbh. Natasha Frank has patent pending to Ticeba Gmbh. Potential Conflict of interest Disclosure: Christoph Ganss: CEO and shareholder of TICEBA GmbH; CEO of RHEACELL GmbH & Co. KG Andreas Kluth: CSO of TICEBA GmbH; CSO of RHEACELL GmbH & Co. KG Christoph Maβlo: Project coordinator of RHEACELL GmbH & Co. KG Potential Conflict of Interest Disclosure: N.Y.F. and M.H.F. are inventors or co-inventor sof US and international patents assigned to Brigham and Women’s Hospital and/or Boston Children’s Hospital, Boston, MA, and licensed to TICEBA GmbH (Heidelberg, Germany) and RHEACELL GmbH & Co. KG (Heidelberg, Germany). M.H.F. serves as a scientific advisor to TICEBA GmbH and RHEACELL GmbH & Co. KG.
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