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Peer-reviewedCC BY 4.0Clinical & Experimental Ophthalmology

VEGF‐A Antisense Oligonucleotide Therapy Inhibits Corneal Neovascularisation and Enhances Graft Survival in Murine High‐Risk Corneal Transplantation

  • Wei Zhang1,2,3
  • Christian Weile4
  • Christoph Ullmer5
  • Sascha Fauser5
  • Felix Bock1,6
  • Claus Cursiefen1,6,7
7 affiliations
  1. 1Department of Ophthalmology University of Cologne, Faculty of Medicine and University Hospital Cologne Cologne Germany
  2. 2Department of Ophthalmology, Hebei Eye Hospital Hebei Key Laboratory of Ophthalmology Xingtai Hebei China
  3. 3Department of Ophthalmology Affiliated Hospital of Guizhou Medical University, Guizhou Medical University Guiyang China
  4. 4BioInnovation Institute Copenhagen Denmark
  5. 5Roche Pharma Research & Early Development Roche Innovation Center Basel, F. Hoffmann‐La Roche Ltd Basel Switzerland
  6. 6Center for Molecular Medicine Cologne (CMMC) University of Cologne Cologne Germany
  7. 7CECAD Cluster of Excellence University of Cologne Cologne Germany
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Abstract

Background: To investigate, for the first time, whether an unconjugated VEGF‐A antisense oligonucleotide (ASO) can inhibit corneal neovascularisation and improve graft survival in a murine high‐risk corneal transplantation model.

Methods: A suture‐induced corneal neovascularisation model was established in BALB/c mice, followed by high‐risk corneal transplantation using C57BL/6 donor corneas. A VEGF‐A RNase H–recruiting ASO (gapmer) was delivered via subconjunctival injection, topical eye drops, or ex vivo preincubation of donor corneas. Blood vessels (BVs) and lymphatic vessels (LVs) were quantified by immunohistochemistry, and Vegfa mRNA expression was measured by qPCR. Immune cell profiles in draining lymph nodes (dLNs), focusing on regulatory T cells (Tregs) and dendritic cells (DCs), were analysed by flow cytometry. Graft survival was monitored for 8 weeks using Kaplan–Meier analysis.

Results: Subconjunctival and topical VEGF‐A ASO administration significantly suppressed corneal hemangiogenesis and lymphangiogenesis (p < 0.05). Subconjunctival injection also induced regression of established vessels (BVs −21.76%, p = 0.0039; LVs −49.75%, p = 0.0110). Graft survival improved significantly after subconjunctival treatment (p = 0.0438) and donor cornea preincubation (p = 0.0148). Flow cytometry showed increased Treg frequency in dLNs following subconjunctival ASO administration (p = 0.0293). Preincubation of donor corneas markedly reduced Vegfa mRNA levels (p < 0.0001).

Conclusions: VEGF‐A–targeting ASO effectively inhibits corneal neovascularisation and improves graft survival in high‐risk transplantation. Local and ex vivo VEGF‐A inhibition using ASO represents a promising therapeutic strategy for controlling ocular neovascularisation and enhancing corneal transplant outcomes.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026vegfa,
  title = {{VEGF‐A Antisense Oligonucleotide Therapy Inhibits Corneal Neovascularisation and Enhances Graft Survival in Murine High‐Risk Corneal Transplantation}},
  author = {Wei Zhang and Christian Weile and Christoph Ullmer and Sascha Fauser and Felix Bock and Claus Cursiefen},
  journal = {Clinical \& Experimental Ophthalmology},
  year = {2026},
  month = sep,
  doi = {10.1111/ceo.70159},
  url = {https://doi.org/10.1111/ceo.70159},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - VEGF‐A Antisense Oligonucleotide Therapy Inhibits Corneal Neovascularisation and Enhances Graft Survival in Murine High‐Risk Corneal Transplantation
AU  - Wei Zhang
AU  - Christian Weile
AU  - Christoph Ullmer
AU  - Sascha Fauser
AU  - Felix Bock
AU  - Claus Cursiefen
PY  - 2026
DA  - 2026/09/09
JO  - Clinical & Experimental Ophthalmology
DO  - 10.1111/ceo.70159
UR  - https://doi.org/10.1111/ceo.70159
AB  - Background: To investigate, for the first time, whether an unconjugated VEGF‐A antisense oligonucleotide (ASO) can inhibit corneal neovascularisation and improve graft survival in a murine high‐risk corneal transplantation model.  Methods: A suture‐induced corneal neovascularisation model was established in BALB/c mice, followed by high‐risk corneal transplantation using C57BL/6 donor corneas. A VEGF‐A RNase H–recruiting ASO (gapmer) was delivered via subconjunctival injection, topical eye drops, or ex vivo preincubation of donor corneas. Blood vessels (BVs) and lymphatic vessels (LVs) were quantified by immunohistochemistry, and Vegfa mRNA expression was measured by qPCR. Immune cell profiles in draining lymph nodes (dLNs), focusing on regulatory T cells (Tregs) and dendritic cells (DCs), were analysed by flow cytometry. Graft survival was monitored for 8 weeks using Kaplan–Meier analysis.  Results: Subconjunctival and topical VEGF‐A ASO administration significantly suppressed corneal hemangiogenesis and lymphangiogenesis (p < 0.05). Subconjunctival injection also induced regression of established vessels (BVs −21.76%, p = 0.0039; LVs −49.75%, p = 0.0110). Graft survival improved significantly after subconjunctival treatment (p = 0.0438) and donor cornea preincubation (p = 0.0148). Flow cytometry showed increased Treg frequency in dLNs following subconjunctival ASO administration (p = 0.0293). Preincubation of donor corneas markedly reduced Vegfa mRNA levels (p < 0.0001).  Conclusions: VEGF‐A–targeting ASO effectively inhibits corneal neovascularisation and improves graft survival in high‐risk transplantation. Local and ex vivo VEGF‐A inhibition using ASO represents a promising therapeutic strategy for controlling ocular neovascularisation and enhancing corneal transplant outcomes.
SN  - 1442-6404
SN  - 1442-9071
ER  -