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Open AccessArticle

Bevacizumab Induces Upregulation of Keratin 3 and VEGFA in Human Limbal Epithelial Cells in Vitro

1
Deptement of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Kerpener Straße 62, 50937 Cologne, Germany
2
Centre for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Straße 21, 50931 Cologne, Germany
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(11), 1925; https://doi.org/10.3390/jcm8111925 (registering DOI)
Received: 19 September 2019 / Revised: 14 October 2019 / Accepted: 7 November 2019 / Published: 9 November 2019
(This article belongs to the Special Issue Corneal Transplant Immunology)
Topical application of vascular endothelial growth factor A (VEGFA) inhibitors including Bevacizumab is used for antiangiogenic therapy at the ocular surface. While clinical studies have suggested that this approach is well-tolerated, the effect of the drug on limbal epithelial stem cells has not been studied. In this study, the effect of Bevacizumab on phenotype and functionality of putative limbal epithelial stem cells (SC) was investigated. The effect of Bevacizumab on human limbal epithelial cells was assessed in terms of metabolic activity and scratch wound closure. The different treatment groups featured no difference in proliferation and colony forming efficiency (CFE) of limbal epithelial cells or their putative SC marker expression. A significant delay in scratch closure of all the Bevacizumab-treated groups was detected at 4 h. RNA and protein quantification indicated a dose-responsive increase of keratin 3. VEGFA RNA expression also increased while VEGFC and D as well as VEGFR1, 2 and 3 were unchanged. This study highlights previously unknown effects of Bevacizumab on cultured putative limbal epithelial SC: a dose-related increase of keratin 3, an increase in VEGFA as well as a delay in scratch wound closure. These in vitro data should be considered when using Bevacizumab in the context of limbal epithelial SC transplantation. View Full-Text
Keywords: Bevacizumab; limbal epithelial cells; stem cells; keratin 3 Bevacizumab; limbal epithelial cells; stem cells; keratin 3
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MDPI and ACS Style

Notara, M.; Lentzsch, A.; Clahsen, T.; Behboudifard, S.; Braun, G.; Cursiefen, C. Bevacizumab Induces Upregulation of Keratin 3 and VEGFA in Human Limbal Epithelial Cells in Vitro. J. Clin. Med. 2019, 8, 1925.

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