Dataset Information

Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age-related macular degeneration.

ABSTRACT:

Background and purpose

The present treatment for choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) is not sufficient. Hence, we examined the therapeutic efficacy of reducing histamine H4 receptor expression on CNV in mice.

Experimental approach

H4 receptor expression was examined in CNVs from patients with AMD. In mice, laser photocoagulation was performed in the retina to induce experimental CNV (laser CNV). Protein and mRNA expression levels were determined and CNV volume measured in wild-type and Hrh4(-/-) mice with laser CNV. The effects of JNJ7777120, an H4 receptor antagonist, administered intravitreously, on CNV volume and pathological vessel leakage were determined in mice with laser CNV and controls. Fundus imaging, retinal histology and electroretinography were performed on eyes injected with JNJ7777120 to evaluate retinal toxicity.

Key results

Human H4 receptors were only confirmed in CNV samples from AMD patients and not in the other subretinal tissues. Mouse H4 receptors were expressed in retinal pigment epithelium only after inducing laser CNV in wild-type mice, and were co-localized with the macrophage marker F4/80. Laser CNV volume was reduced in Hrh4(-/-) mice compared with that in wild-type mice, and JNJ7777120 suppressed laser-induced CNV volume and pathological CNV leakage in wild-type mice. Also eyes injected with JNJ7777120 did not show retinal degeneration.

Conclusions and implications

H4 receptors are expressed in macrophages that accumulate around CNVs. Suppressing H4 receptor expression prevented the pathological vessel leakage without showing retinal toxicity, indicating that the H4 receptor has potential as a novel therapeutic target in AMD.

SUBMITTER: Kaneko H

PROVIDER: S-EPMC4128071 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age-related macular degeneration.

Kaneko Hiroki H Ye Fuxiang F Ijima Ryo R Kachi Shu S Kato Seiichi S Nagaya Masatoshi M Higuchi Akiko A Terasaki Hiroko H

British journal of pharmacology 20140801 15

<h4>Background and purpose</h4>The present treatment for choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) is not sufficient. Hence, we examined the therapeutic efficacy of reducing histamine H4 receptor expression on CNV in mice.<h4>Experimental approach</h4>H4 receptor expression was examined in CNVs from patients with AMD. In mice, laser photocoagulation was performed in the retina to induce experimental CNV (laser CNV). Protein and mRNA expression leve ...[more]

PMID: 24787705

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Project description:PURPOSE:To detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography. DESIGN:Observational, cross-sectional study. PARTICIPANTS:A total of 5 normal subjects and 5 subjects with neovascular AMD were included. METHODS:A total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3 × 3-mm area and comprised 200 × 200 × 8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. MAIN OUTCOME MEASURES:The CNV angiogram, CNV area, and CNV flow index. RESULTS:En face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV. CONCLUSIONS:Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

Dataset Information

Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age-related macular degeneration.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age-related macular degeneration.

Similar Datasets

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