First Author | Toriyama Y | Year | 2015 |
Journal | Am J Pathol | Volume | 185 |
Issue | 6 | Pages | 1783-94 |
PubMed ID | 25857228 | Mgi Jnum | J:221180 |
Mgi Id | MGI:5638466 | Doi | 10.1016/j.ajpath.2015.02.017 |
Citation | Toriyama Y, et al. (2015) Pathophysiological function of endogenous calcitonin gene-related Peptide in ocular vascular diseases. Am J Pathol 185(6):1783-94 |
abstractText | 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)-alpha production were enhanced within the CNV lesions in CGRP(-/-) mice, and the TNF-alpha, 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-alpha 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. |