Transient postoperative vascular endothelial growth factor (VEGF)-neutralisation improves graft survival in corneas with partly regressed inflammatory neovascularisation
- B O Bachmann1,2,
- E Luetjen-Drecoll1,
- F Bock2,
- S J Wiegand3,
- D Hos1,
- R Dana4,
- F E Kruse2,
- C Cursiefen2,4
- 1Department of Anatomy II, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
- 2Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
- 3Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA
- 4Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
- Correspondence to Dr C Cursiefen, Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany;
- Accepted 22 January 2009
- Published Online First 17 February 2009
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.
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.