Endothelins-1 and 3 (ET-1 and 3) were evaluated for angiogenesis in the rat cornea. Bisected 2 mm pellets containing 20-1000 ng of ET-1 or ET-3 in Hydron were placed in corneal micro-pockets. Murine vascular endothelial growth factor (VEGF) and human interleukin-8 (IL-8) were positive controls. No angiogenesis occurred in 32 corneas with pellets containing only saline. With 200 ng VEGF pellets, 27/52 corneas (52%) demonstrated angiogenesis. With 200 ng IL-8 pellets, 32/51 corneas (63%) demonstrated angiogenesis. With 20-1000 ng ET-1 pellets, angiogenesis occurred in 65/91 corneas (71%); with ET-3 pellets, 84/116 (72%). ET-1- and ET-3-mediated angiogenesis was unaffected by cyclophosphamide-induced leukopenia. ET-1-mediated angiogenesis was inhibited by an ETA-receptor antagonist (ra) (BQ610) and a combined ETA/ETB ra (bosentan). However, ET-1-mediated angiogenesis was not inhibited by an ETB ra(BQ788) and a weak ETA ra(BQ123). Thus, ET-1 and -3 are angiogenic in the rat cornea; this effect appears to be direct, not leukocyte-mediated, and ETA-receptor-dependent.
*Departments of Surgery and Physiology, Michael Reese Hospital and Medical Center and the University of Illinois at Chicago, College of Medicine, Chicago, Illinois, and †Departments of Surgery and Critical Care, Montefiore Hospital and Medical Center, Albert Einstein University Medical School, New York, U.S.A.
Address correspondence and reprint requests to Marvin A. McMillen, Department of Surgery, Montefiore Hospital and Medical Center, 111 E. 210 St., New York, NY 10467, U.S.A. E-mail: [email protected]
© 2000 Lippincott Williams & Wilkins, Inc.