title: Adrenomedullin: A potential therapeutic target for retinochoroidal disease.
abstract: Adrenomedullin (AM) is a 52-amino acid peptide with anti-inflammatory, anti-apoptotic, and anti-oxidative properties discovered in a human pheochromocytoma. It is a member of the calcitonin peptide superfamily, and its signal is mediated by calcitonin receptor-like receptor (CLR). CLR interacts with receptor activity-modifying proteins (RAMPs), among which RAMP-2 and RAMP-3 carry CLR from the endoplasmic reticulum to the cellular membrane to confer high affinity for AM. In addition to being implicated in a variety of systemic diseases, AM is a critical contributor to the pathogenesis of retinochoroidal disease. It is robustly upregulated in retinochoroidal disease models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularisation (CNV) as well as in human patients with retinochoroidal diseases. In this review, we discuss the most salient recent findings that strongly illustrate the role of AM in retinochoroidal disease. In the OIR model, AM was identified as a key angiogenic mediator of retinal vascularisation, and AM inhibition suppressed only pathological angiogenesis, not physiological angiogenesis. On the contrary, lesion size was larger in AM(+/-) CNV model mice, presumably due to the anti-inflammatory function of AM. Despite the success of anti-vascular endothelial growth factor agents for the treatment of retinochoroidal disease, therapeutic shortcomings remain. Finding ways to modulate AM activity will provide new treatment avenues. Potential treatment strategies modulating the action of AM and its signaling pathway have been studied extensively. AM and its signaling molecules are intriguing future treatment targets for retinochoroidal disease.
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iesato
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yuda
authors.affiliation: Singapore National Eye Centre, Singapore, Singapore.
authors.forename: Kelvin Teo Yi
authors.initials: KT
authors.lastname: Chong
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Xue
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shindo
authors.affiliation: Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore. Electronic address: yanagi-tky@umin.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
mesh_terms: D053607:Adrenomedullin / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D000818:Animals; D058286:Calcitonin Receptor-Like Protein; D015862:Choroid Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D015398:Signal Transduction / Q000502:physiology
chemical_list: D058286:Calcitonin Receptor-Like Protein; D053607:Adrenomedullin
keywords: Adrenomedullin; Calcitonin gene-related peptide; Choroidal neovascularisation; Oxygen-induced retinopathy; Receptor activity-modifying protein