Artikel
Does inhibition of hem- and lymphangiogenesis after normal-risk corneal transplantation improve graft survival?
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Autoren
Veröffentlicht: | 22. September 2004 |
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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)