gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Does inhibition of hem- and lymphangiogenesis after normal-risk corneal transplantation improve graft survival?

Meeting Abstract

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  • corresponding author C. Cursiefen - Augenklinik mit Poliklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogSA.14.07

The electronic version of this article is the complete one and can be found online at:

Published: September 22, 2004

© 2004 Cursiefen.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.




To evaluate the feasibility of the new concept of improving corneal graft survival by modulating hem- and lymphangiogenesis after keratoplasty. Occurrence and time course of hem- and lymphangiogenesis after normal-risk corneal transplantation in the mouse model and the effect of pharmacologic strategies inhibiting both processes on long-term graft survival were analyzed.


Normal-risk allogeneic (C57BL/6 to BALB/c) and syngeneic (BALB/c to BALB/c) corneal transplantations were performed and occurrence and time course of hem- and lymphangiogenesis after keratoplasty was observed using double immunofluorescence of corneal flatmounts (with CD31 as panendothelial and LYVE-1 as lymphatic vascular endothelial specific marker). A molecular trap designed to eliminate VEGF-A (VEGF TrapR1R2; 12.5 mg/kg) was tested for its ability to inhibit both processes after keratoplasty and to promote long-term graft survival (intraperitoneal injections on the day of surgery and 3, 7, and 14 days later).


No blood or lymph vessels were detectable immediately after normal-risk transplantation in either donor or host cornea, but hem- and lymphangiogenesis were clearly visible at day 3 after transplantation. Both vessel types reached donor tissue at one week after allo- and similarly after syngeneic grafting. Early postoperative trapping of VEGF-A significantly reduced both hem- and lymphangiogenesis and significantly improved long-term graft survival (78% versus 40%; p<0.05).


There is concurrent, hem- and lymphangiogenesis after normal-risk keratoplasty within the preoperatively avascular recipient bed. Inhibition of hem- and lymphangiogenesis (afferent and efferent arm of an immune response) after normal-risk corneal transplantation improves long-term graft survival, establishing early postoperative hem- and lymphangiogenesis as novel risk factors for graft rejection even in low-risk eyes. This study provides proof-of-principle that modulation of hem- and lymphangiogenesis after normal-risk keratoplasty can improve corneal graft survival.


DFG (Cu 47/1-1; Cu 47/1-2), IZKF Erlangen (A9)