title: Pathophysiological function of endogenous calcitonin gene-related peptide in ocular vascular diseases.
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.
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan; Department of Ophthalmology, Shinshu University School of Medicine, Nagano, Japan.
authors: Yuichi
authors: Y
authors: Toriyama
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan; Department of Ophthalmology, Shinshu University School of Medicine, Nagano, Japan.
authors: Yasuhiro
authors: Y
authors: Iesato
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan; Department of Ophthalmology, Shinshu University School of Medicine, Nagano, Japan.
authors: Akira
authors: A
authors: Imai
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Takayuki
authors: T
authors: Sakurai
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Akiko
authors: A
authors: Kamiyoshi
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Yuka
authors: Y
authors: Ichikawa-Shindo
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Hisaka
authors: H
authors: Kawate
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Akihiro
authors: A
authors: Yamauchi
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Kyoko
authors: K
authors: Igarashi
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Megumu
authors: M
authors: Tanaka
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Tian
authors: T
authors: Liu
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Xian
authors: X
authors: Xian
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Liuyu
authors: L
authors: Zhai
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan.
authors: Shinji
authors: S
authors: Owa
authors: Department of Ophthalmology, Shinshu University School of Medicine, Nagano, Japan.
authors: Toshinori
authors: T
authors: Murata
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Nagano, Japan. Electronic address: tshindo@shinshu-u.ac.jp.
authors: Takayuki
authors: T
authors: Shindo
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology
chemical_list: D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide