title: CCR3 and 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-A) in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin) targeting for CNV.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.forename: Deqiang
authors.initials: D
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Xia
authors.forename: Zhengying
authors.initials: Z
authors.lastname: Wang
authors.forename: Lingyu
authors.initials: L
authors.lastname: Luo
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D020256:Choroidal Neovascularization / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D003094:Collagen; D004195:Disease Models, Animal; D004338:Drug Combinations; D007797:Laminin; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods; D009281:Naphthalenes / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011509:Proteoglycans; D051381:Rats; D017207:Rats, Sprague-Dawley; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D004338:Drug Combinations; D007797:Laminin; D009281:Naphthalenes; D011509:Proteoglycans; D054397:Receptors, CCR3; C417503:SB 328437; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D010649:Phenylalanine; D003094:Collagen; D058570:TOR Serine-Threonine Kinases