The Blockade of Vascular Endothelial Growth Factor C Effectively Inhibits Corneal Lymphangiogenesis and Promotes Allograft Survival.

Abstract

To explore the inhibitory effects of antivascular endothelial growth factor C (VEGF-C) therapy on corneal lymphangiogenesis and allograft rejection in rats. Fischer 344 rat corneas were transplanted into Lewis rat eyes. After corneal transplantation, Lewis rats (the recipients) were randomly and equally divided into 2 groups: anti-VEGF-C treatment (group A) and control (group B). Corneal hemangiogenesis and lymphangiogenesis were characterized using whole-mount immunofluorescence, and the immune rejection of the grafts was examined using a slit lamp and evaluated by scoring the rejection index (RI). In addition, the expression of VEGF-C was examined by immunohistochemistry and real-time polymerase chain reaction. The association of corneal lymphangiogenesis and hemangiogenesis with VEGF-C in transplanted corneas was also characterized. VEGF-C expression was markedly downregulated after anti-VEGF-C therapy. The outgrowth of corneal lymphangiogenesis dramatically decreased in group A. There was a significant relationship between VEGF-C reduction and the decrease in the lymphatic vessel area (r=0.55, P<0.05), whereas the relationship between the reduction of VEGF-C and the decrease in blood vessel area was not significant (r=0.11, P>0.05). In addition, the RI scores were significantly lower in group A compared with group B at 7, 10, and 14 days after transplantation. The graft survival time in group A rats (20.33±1.37 days) was significantly longer than that in group B rats (12.83±1.47 days; P<0.05). The results suggested that VEGF-C blockade had a significant role in preventing corneal lymphangiogenesis in corneal beds, which resulted in higher allograft survival rates.