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Laboratory science
Transient postoperative vascular endothelial growth factor (VEGF)-neutralisation improves graft survival in corneas with partly regressed inflammatory neovascularisation
  1. B O Bachmann1,2,
  2. E Luetjen-Drecoll1,
  3. F Bock2,
  4. S J Wiegand3,
  5. D Hos1,
  6. R Dana4,
  7. F E Kruse2,
  8. C Cursiefen2,4
  1. 1
    Department of Anatomy II, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
  2. 2
    Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
  3. 3
    Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA
  4. 4
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr C Cursiefen, Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany; ccursiefen{at}yahoo.com

Abstract

Background: High-risk keratoplasties are usually performed after an uninflamed and quiescent interval in corneas with partly regressed blood and lymphatic vessels. We analysed whether the inhibition of post-keratoplasty revascularisation in mice with partly regressed corneal vessels (“intermediate-risk”) improves graft survival.

Methods: Three interrupted stromal sutures (11-0) in corneas of Balb/c mice (6–8 weeks old) were placed for 6 weeks. Six months after suture removal, penetrating keratoplasty was performed with C57BL/6 donors. The treatment group received a vascular endothelial growth factor-A specific cytokine trap (VEGF Trap) intraperitoneally at days 0, 4, 7 and 14 after keratoplasty (25 mg/kg per mouse; controls received equal amounts of Fc protein). Pathological haemangiogenesis and lymphangiogenesis prior to as well as 3 days or 8 weeks after keratoplasty and graft survival were analysed.

Results: Three days after keratoplasty corneal revascularisation was sufficiently reduced by VEGF Trap (haem-vascularised areas 42.7% reduction; lymph-vascularised areas 54.7% reduction). Survival proportions 8 weeks after keratoplasty were 36% in the treatment group compared with 9% in the control group (n = 11; p<0.05). At that time no differences in haemangiogenesis or lymphangiogenesis were observed between the two groups.

Conclusion: Early transient postoperative induction of haemangiogenesis and lymphangiogenesis and reformation of regressed corneal blood and lymphatic vessels are important for transplant rejections after “intermediate-risk” corneal transplantation.

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Footnotes

  • Funding German Research Council (Deutsche Forschungsgemeinschaft Grants Cu 47/1-1 and Cu 47/1-2), National Eye Institute (Grant EY10765), Interdisciplinary Center for Clinical Research (IZKF) Erlangen (Project A9 and “Rotation Grant” (B O Bachman)), ELAN fund for Science and Teaching Erlangen.

  • Competing interests VEGF Trap was provided by Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.

  • Ethics approval All animals were treated in accordance with the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research.

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