Pathophysiological function of endogenous calcitonin gene-related peptide in ocular vascular diseases.
Am J Pathol
; 185(6): 1783-94, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25857228
ABSTRACT
Calcitonin gene-related peptide (CGRP; official name CALCA) has a variety of functions and exhibits both angiogenic and anti-inflammatory properties. We previously reported the angiogenic effects of the CGRP family peptide adrenomedullin in oxygen-induced retinopathy; however, the effects of CGRP on ocular angiogenesis remain unknown. Herein, we used CGRP knockout (CGRP(-/-)) mice to investigate the roles of CGRP in ocular vascular disease. Observation of pathological retinal angiogenesis in the oxygen-induced retinopathy model revealed no difference between CGRP(-/-) and wild-type mice. However, much higher levels of the CGRP receptor were present in the choroid than the retina. Laser-induced choroidal neovascularization (CNV), a model of exudative age-related macular degeneration, revealed more severe CNV lesions in CGRP(-/-) than wild-type mice, and fluorescein angiography showed greater leakage from CNV in CGRP(-/-). In addition, macrophage infiltration and tumor necrosis factor (TNF)-α production were enhanced within the CNV lesions in CGRP(-/-) mice, and the TNF-α, in turn, suppressed the barrier formation of retinal pigment epithelial cells. In vivo, CGRP administration suppressed CNV formation, and CGRP also dose dependently suppressed TNF-α production by isolated macrophages. From these data, we conclude that CGRP suppresses the development of leaky CNV through negative regulation of inflammation. CGRP may thus be a promising therapeutic agent for the treatment of ocular vascular diseases associated with inflammation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Retina
/
Vasos Retinianos
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Peptídeo Relacionado com Gene de Calcitonina
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Neovascularização de Coroide
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article