Universität zu Köln

Chen, Zhe ORCID: 0000-0002-7627-1697, Zhang, Wei, Mestanoglu, Mert ORCID: 0000-0002-7984-5959, Cursiefen, Claus ORCID: 0000-0002-1958-411X and Bock, Felix ORCID: 0000-0002-5691-8289 (2025). Promotion of vessel regression by local VEGF-A blockade improves the survival rate of corneal transplants. Experimental Eye Research, 261. pp. 1-9. Elsevier. ISSN 0014-4835

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Abstract

[Artikel-Nr.: 110652] To primarily evaluate the efficacy of different topical vascular endothelial growth factor (VEGF) blocking treatments, namely Aflibercept and Bevacizumab, in promoting regression of pathologic corneal neovascularization (NV) and secondarily to investigate their effects on graft survival in a high-risk mouse corneal transplantation model. In addition, the immune modulatory effects were assessed. After 14 days of suture-induced, inflammatory corneal NV, sutures were removed. Anti-VEGF eye drops or vehicle controls were applied topically 3 times daily for one week. After 21 days, the regression of blood vessels (BVs) and lymphatic vessels (LVs) was assessed via immunofluorescence staining. In addition, corneal grafting was performed in another set of mice. Therefore, allogeneic donor corneas from C57BL/6N mice were used and graft survival was monitored weekly for 8 weeks. Finally, hem-and lymphangiogenesis as well as the phenotype of antigen-presenting cells (APCs) in draining lymph nodes (dLNs) and corneas were analyzed by immunohistochemistry and FACS, respectively. Both, Aflibercept and Bevacizumab eye drops supported the regression of both blood and lymphatic vessels. Aflibercept-treated corneas demonstrated decreased APC activation in the dLNs after treatment at day 21. In the high-risk transplantation model, both therapeutics could improve graft survival rates (Aflibercept: 60 %, P = 0.0091; Bevacizumab: 50 %, P = 0.0547) compared to control (10 %). Eight weeks post-transplantation, both treatment arms displayed decreased APC recruitment and an increased expression of Foxp3 on CD4+CD25+ T cells. Our study demonstrates that different topically applied anti-VEGF eye drops effectively reduce pre-existing corneal neovascularization and thereby improve subsequent high-risk corneal transplantation. This translational approach could become a promising strategy to improve the clinical outcome of high risk keratoplasty in patients.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Chen, Zhe UNSPECIFIED https://orcid.org/0000-0002-7627-1697 UNSPECIFIED Zhang, Wei UNSPECIFIED UNSPECIFIED UNSPECIFIED Mestanoglu, Mert UNSPECIFIED https://orcid.org/0000-0002-7984-5959 UNSPECIFIED Cursiefen, Claus UNSPECIFIED https://orcid.org/0000-0002-1958-411X UNSPECIFIED Bock, Felix UNSPECIFIED https://orcid.org/0000-0002-5691-8289 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-810304
Identification Number:	10.1016/j.exer.2025.110652
Journal or Publication Title:	Experimental Eye Research
Volume:	261
Page Range:	pp. 1-9
Number of Pages:	9
Date:	December 2025
Publisher:	Elsevier
ISSN:	0014-4835
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Augenheilkunde > Klinik und Poliklinik für Allgemeine Augenheilkunde
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Neovascularization regression ; Aflibercept ; Bevacizumab ; Corneal transplantation ; Immune modulation English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81030