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

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dog2004/04dog402.shtml

Veröffentlicht: 22. September 2004

© 2004 Cursiefen.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

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.

Methods

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).

Results

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).

Conclusions

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.

Support

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