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Open AccessArticle
Selective, Temporary Postoperative Inhibition of Lymphangiogenesis by Integrin α5β1 Blockade Improves Allograft Survival in a Murine Model of High-Risk Corneal Transplantation
by
Tina Dietrich-Ntoukas
Tina Dietrich-Ntoukas 1,2,*
,
Felix Bock
Felix Bock 3,
Jasmine Onderka
Jasmine Onderka 2,
Deniz Hos
Deniz Hos 3,
Bjoern O. Bachmann
Bjoern O. Bachmann 3,
Grit Zahn
Grit Zahn 4 and
Claus Cursiefen
Claus Cursiefen 3
1
Department of Ophthalmology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353 Berlin, Germany
2
Department of Ophthalmology, University Erlangen-Nürnberg, 91054 Erlangen, Germany
3
Department of Ophthalmology, University Hospital of Cologne, 50937 Cologne, Germany
4
Eternygen GmbH, 10178 Berlin, Germany
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2024, 13(15), 4418; https://doi.org/10.3390/jcm13154418 (registering DOI)
Submission received: 30 May 2024
/
Revised: 5 July 2024
/
Accepted: 25 July 2024
/
Published: 28 July 2024
Abstract
Background: Corneal inflammatory hem- and lymphangiogenesis significantly increase the risk for immune rejection after subsequent allogeneic corneal transplantation. The purpose of this study was to analyze the impact of temporary selective inhibition of lymphangiogenesis after transplantation on graft survival. Methods: Allogeneic transplantation from C57BL/6 mice to BalbC mice was performed as “high-risk” keratoplasty in a prevascularized corneal host bed (suture-induced inflammatory corneal neovascularization). The treatment group received integrin α5β1-blocking small molecules (JSM6427) at the time of transplantation and for two weeks afterwards. Control mice received a vehicle solution. Grafts were evaluated weekly for graft rejection using an opacity score. At the end of the follow-up, immunohistochemical staining of corneal wholemounts for lymphatic vessels as well as CD11b+ immune cells was performed. Results: Temporary postoperative inhibition of lymphangiogenesis by JSM6427 improved the corneal graft survival significantly. At the end of the follow-up, no significant reduction in CD11b+ immunoreactive cells within the graft compared to controls was found. Conclusions: The significant improvement of corneal graft survival by the selective, temporary postoperative inhibition of lymphangiogenesis after keratoplasty using integrin antagonists shows the impact of lymphatic vessels in the early postoperative phase. Retarding lymphatic vessel ingrowth into the graft might be sufficient for the shift to immunological tolerance in the postoperative period, even after high-risk keratoplasty.
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MDPI and ACS Style
Dietrich-Ntoukas, T.; Bock, F.; Onderka, J.; Hos, D.; Bachmann, B.O.; Zahn, G.; Cursiefen, C.
Selective, Temporary Postoperative Inhibition of Lymphangiogenesis by Integrin α5β1 Blockade Improves Allograft Survival in a Murine Model of High-Risk Corneal Transplantation. J. Clin. Med. 2024, 13, 4418.
https://doi.org/10.3390/jcm13154418
AMA Style
Dietrich-Ntoukas T, Bock F, Onderka J, Hos D, Bachmann BO, Zahn G, Cursiefen C.
Selective, Temporary Postoperative Inhibition of Lymphangiogenesis by Integrin α5β1 Blockade Improves Allograft Survival in a Murine Model of High-Risk Corneal Transplantation. Journal of Clinical Medicine. 2024; 13(15):4418.
https://doi.org/10.3390/jcm13154418
Chicago/Turabian Style
Dietrich-Ntoukas, Tina, Felix Bock, Jasmine Onderka, Deniz Hos, Bjoern O. Bachmann, Grit Zahn, and Claus Cursiefen.
2024. "Selective, Temporary Postoperative Inhibition of Lymphangiogenesis by Integrin α5β1 Blockade Improves Allograft Survival in a Murine Model of High-Risk Corneal Transplantation" Journal of Clinical Medicine 13, no. 15: 4418.
https://doi.org/10.3390/jcm13154418
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