What is the role of CCR3 in choroidal neovascularization?

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet" AMD, characterized by the development of choroidal neovacularization (CNV), could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF) in CNV development has been clearly demonstrated and clinically VEGF neutralization has become standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and CCR3 targeting was believed to be superior to VEGF targeting for CNV suppression. Our data in the present work show that blocking CCR3 by a small molecule CCR3 antagonist SB 328437 or CCR3-neutralizing antibodies does not inhibit CNV in the Matrigel CNV models of rat and mouse, whereas VEGF-neutralizing antibodies or rapamycin effectively suppresses CNV. These results question the role of CCR3 in CNV development and the therapeutic approach to suppress CNV by CCR3 targeting. © 2012 Springer Science+Business Media, LLC.