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Transient postoperative VEGF-neutralisation improves graft survival in corneas with partly regressed inflammatory neovascularisation
  1. Bjoern O Bachmann (bachmann_bjoern{at}web.de),
  2. Elke Luetjen-Drecoll (drecoll{at}anatomie2.med.uni-erlangen.de),
  3. Felix Bock (felix.bock{at}uk-erlangen.de),
  4. Stanley J Wiegand (stanley.wiegand{at}regeneron.com),
  5. Deniz Hos (hosdeniz{at}yahoo.de),
  6. Reza Dana (reza.dana{at}schepens.harvard.edu),
  7. Friedrich E Kruse (friedrich.kruse{at}uk-erlangen.de),
  8. Claus Cursiefen (ccursiefen{at}yahoo.com)
  1. Department of Ophthalmology, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
  2. Department of Anatomy II, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
  3. Department of Ophthalmology, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
  4. Regeneron Pharmaceuticals Inc., United States
  5. Department of Ophthalmology, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
  6. Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Germany
  7. Department of Ophthalmology, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany
  8. Department of Ophthalmology, Friedrich-Alexander-University of Erlangen-Nuremberg, Germany

    Abstract

    Background: High-risk keratoplasties normally are performed after an uninflamed and quiescent interval in corneas with partly regressed blood and lymphatic vessels. We analysed whether the inhibition of postkeratoplasty 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) were placed for 6 weeks. Six months after suture removal, penetrating keratoplasty was performed with C57BL/6 donors. The treatment group received a VEGF-A specific cytokine trap (VEGF Trap) intraperitoneally at days 0, 4, 7 and 14 after keratoplasty (25 mg/kg/mouse; controls received equal amounts Fc-protein). Pathological hem- and lymphangiogenesis prior to as well as three days or 8 weeks after keratoplasty and graft survival were analysed.

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

    Conclusion: Early transient postoperative induction of hem- 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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