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CCR3 and choroidal neovascularization
- Source :
- PLoS ONE, Vol 6, Iss 2, p e17106 (2011), PLoS ONE
- Publication Year :
- 2011
- Publisher :
- Public Library of Science (PLoS), 2011.
-
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.
- Subjects :
- Vascular Endothelial Growth Factor A
Mouse
genetic structures
Cancer Treatment
lcsh:Medicine
Cardiovascular
Rats, Sprague-Dawley
Mice
0302 clinical medicine
immune system diseases
Drug Discovery
Molecular Targeted Therapy
lcsh:Science
Mice, Inbred BALB C
0303 health sciences
Multidisciplinary
TOR Serine-Threonine Kinases
hemic and immune systems
Animal Models
Sprague dawley
Drug Combinations
medicine.anatomical_structure
Choroidal neovascularization
Oncology
Medicine
Cytokines
Retinal Disorders
Proteoglycans
Antiangiogenesis Therapy
Collagen
medicine.symptom
Research Article
Drugs and Devices
medicine.medical_specialty
Drug Research and Development
Phenylalanine
Receptors, CCR3
Naphthalenes
Biology
Models, Biological
Rats sprague dawley
03 medical and health sciences
Model Organisms
Vascular Biology
Ophthalmology
medicine
Animals
030304 developmental biology
Extramural
lcsh:R
Macular degeneration
medicine.disease
Antibodies, Neutralizing
Choroidal Neovascularization
eye diseases
Rats
Disease Models, Animal
Immune System
Macular Disorders
Immunology
030221 ophthalmology & optometry
Rat
Clinical Immunology
lcsh:Q
Laminin
Choroid
sense organs
Antibody therapy
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 6
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....528df0c60088c4c47d57b0a49f3ecee3