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R.o. Ijima, Hiroki Kaneko, Fuxiang Ye, K.i. Takayama, Yosuke Nagasaka, Keiko Kataoka, Yasuhito Funahashi, Takeshi Iwase, S.u. Kachi, Seiichi Kato, Hiroko Terasaki; Suppression of Laser-Induced Choroidal Neovascularization by the Oral Medicine Targeting Histamine Receptor H4 in Mice. Trans. Vis. Sci. Tech. 2015;4(2):6. doi: https://doi.org/10.1167/tvst.4.2.6.
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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.
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 and Hrh4−/− mice. The long-acting HRH4 antagonist JNJ28307474 was then administrated periorally, and the laser-CNV volume was compared with controls.
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 of Hrh4−/− mice than in wild-type mice. Oral administration of JNJ28307474 significantly reduced laser-CNV volume in wild-type mice.
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.
Translational Relevance: :
Our results indicate that drugs targeting HRH4 are potentially a novel oral treatment for age-related macular degeneration.
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