ROLE OF ICAM-1-MEDIATED LEUKOCYTE ADHESION IN EARLY ANGIOGENESIS IN-VIVO
M. Becker, F.E. Kruse, L. Azzam, R. Nobiling1, M.M. Gebhard1, J. Reichling2
Purpose: Numerous investigations have stressed the significance of leukocytes in early angiogenesis: Leukocytes invade the cornea and the location of their extravasation corresponds to the site of vessel ingrowth. To evaluate the ICAM-1 mediated interaction of leukocytes and vascular endothelium during early corneal angiogenesis we studied the leukocyte adhesion with high-resolution fluorescence angiography in vivo (1).
Methods: Corneal neovascularizations were induced in NZW-rabbits by use of intrastromal pellets containing 750 ng vascular endothelial growth factor (VEGF). Rhodamine 6G was used as fluorescent dyes to stain leukocytes. Leukocyte adhesion and vessel growth were quantified in vivo. To inhibit leukocyte adhesion we applied topically a microemulsion containing anti-ICAM-1.
Results: 24 h following pellet implantation limbal vessels showed increased leukocyte adhesion: Both the number of rolling and sticking leukocytes was significantly increased (p<0.01). Treatment with anti- ICAM-1 resulted in reduced leukocyte sticking and increased leukocyte rolling. The area covered by new blood vessels was significantly diminished in eyes treated with anti-ICAM-1.
Conclusions: Our results support the hypothesis that ICAM-1 mediated leukocyte adhesion is a key event in early angiogenesis. Our model may serve to investigate the significance of adhesion molecules by in vivo observation and quantification.
Department of Ophthalmology, Institute of Experimental Surgery1 , Institute of Pharmaceutical Biology2, University of Heidelberg, D-69120 Heidelberg