title: Suppression of Laser-Induced Choroidal Neovascularization by the Oral Medicine Targeting Histamine Receptor H4 in Mice.
abstract: OBJECTIVE
  This study aimed to examine relationship of histamine receptor H4 (HRH4) and the pathogenesis of laser-induced choroidal neovascularization (laser-CNV) and to determine whether oral administration of HRH4 antagonists suppressed laser-CNV in mice.
  
  
  METHODS
  Laser photocoagulation was performed in mice to induce the laser-CNV. Histamine was administered intravitreously, and CNV volume was measured. Laser photocoagulation and intravitreous injection of HRH4 antagonist JNJ7777120 were performed after intraperitoneal injection of clodronate liposome, which depletes circulating monocyte-derived macrophages; CNV volume was compared with that in mice injected with control (dimethyl sulfoxide [DMSO]/PBS). Three days after laser-CNV, the F4/80+CD11b+macrophage population in retinal pigment epithelium (RPE)/choroid complex was quantified with flow cytometry in wild-type andHrh4-/-mice. The long-acting HRH4 antagonist JNJ28307474 was then administrated periorally, and the laser-CNV volume was compared with controls.
  
  
  RESULTS
  Intravitreous injection of histamine did not affect laser-CNV volume. The laser-CNV from the eye injected with JNJ7777120 was equivalent to that injected with the DMSO/PBS in mice that had intraperitoneally received clodronate liposome. Flow cytometry after laser-CNV induction revealed a smaller F4/80+CD11b+macrophage population in the RPE/choroid complex ofHrh4-/-mice than in wild-type mice. Oral administration of JNJ28307474 significantly reduced laser-CNV volume in wild-type mice.
  
  
  CONCLUSIONS
  Our results suggested that HRH4-positive macrophages played an important role in the pathogenesis of laser-CNV and that they require a different ligand from that of histamine. The oral administration of an HRH4 antagonist successfully reduced laser-CNV.
  
  
  CONCLUSIONS
  Our results indicate that drugs targeting HRH4 are potentially a novel oral treatment for age-related macular degeneration.
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ijima
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kaneko
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nagasaka
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Funahashi
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwase
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Kachi
authors.affiliation: Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Terasaki
keywords: age-related macular degeneration; choroidal neovascularization; histamine receptor H4; macrophage