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Pathophysiological Function of Endogenous Calcitonin Gene–Related Peptide in Ocular Vascular Diseases
- Source :
- American Journal of Pathology; June 2015, Vol. 185 Issue: 6 p1783-1794, 12p
- Publication Year :
- 2015
-
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.
Details
- Language :
- English
- ISSN :
- 00029440
- Volume :
- 185
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- American Journal of Pathology
- Publication Type :
- Periodical
- Accession number :
- ejs35267490
- Full Text :
- https://doi.org/10.1016/j.ajpath.2015.02.017