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Updated: May 14, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Suppression of laser-induced choroidal neovascularization by a CCR3 antagonist
Takeshi Mizutani1, Masayuki Ashikari, Mayumi Tokoro
1Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Purpose:
To evaluate the efficacy of a novel CCR3 antagonist for laser injury-induced choroidal neovascularization (CNV) in mice.
Methods:
We evaluated YM-344031, a novel and selective small-molecule CCR3 antagonist. CNV was induced by laser injury in C57BL/6J mice, and its volume was measured after 7 days by confocal microscopy. Leakage from the CNV was also measured after 7 days by fluorescein angiography. The CCR3 antagonist was administered by gavage at 1 hour before and 1 day after the laser injury, or intravitreous injection immediately after the laser injury. After the laser injury, ELISA, Western blot analysis, and real-time RT-PCR for VEGF-A expression in the RPE/choroid, and immunohistochemistry for CCR3, CCL11, Ki67, and Rac1 was performed.
Results:
Both oral administration and intravitreous injection of YM-344031 significantly suppressed the CNV volume (P < 0.0001 and P < 0.01, respectively). Pathologically significant leakage was significantly less common in YM-344031-injected mice (P < 0.0001). The mean VEGF protein level was significantly increased in vehicle-injected eyes after the laser injury (P < 0.05). Although the YM-344031-injected eyes did not show VEGF-A suppression after the laser injury, VEGF164 mRNA upregulation was significantly suppressed in YM-344031-injected mice (P < 0.05), and intravitreous injection of YM-344031 appeared to suppress CCR3, CCL11 (eotaxin), Ki67, and Rac1 expression after the laser injury.
Conclusions:
The present data suggest that the CCR3 antagonist YM-344031 can suppress CNV, via suppression of the upregulation of VEGF164 mRNA in VEGF isoform after the laser injury. Although our findings may warrant further investigation, YM-344031 may have potential as a new therapy for age-related macular degeneration.
Insights
A novel CCR3 antagonist, YM-344031, effectively reduced choroidal neovascularization (CNV) and leakage in mice. This compound shows potential for treating age-related macular degeneration.
Area of Science:
- Ophthalmology
- Immunology
- Pharmacology
Background:
- Choroidal neovascularization (CNV) is a key pathology in age-related macular degeneration (AMD).
- CCR3 (C-C chemokine receptor type 3) and its ligand CCL11 (eotaxin) are implicated in inflammatory processes relevant to CNV.
- Targeting CCR3 may offer a novel therapeutic strategy for CNV.
Purpose of the Study:
- To evaluate the efficacy of YM-344031, a novel small-molecule CCR3 antagonist, in a mouse model of laser-induced CNV.
- To assess the impact of YM-344031 on CNV volume, leakage, and related molecular markers.
Main Methods:
- CNV was induced by laser injury in C57BL/6J mice.
- YM-344031 was administered orally or via intravitreous injection.
- CNV volume and leakage were quantified using confocal microscopy and fluorescein angiography.
- VEGF-A, CCR3, CCL11, Ki67, and Rac1 expression levels were analyzed via ELISA, Western blot, RT-PCR, and immunohistochemistry.
Main Results:
- Both oral and intravitreous administration of YM-344031 significantly suppressed CNV volume and leakage.
- While total VEGF-A protein levels increased post-injury, YM-344031 significantly suppressed VEGF164 mRNA upregulation.
- YM-344031 treatment appeared to reduce expression of CCR3, CCL11, Ki67, and Rac1.
Conclusions:
- The CCR3 antagonist YM-344031 demonstrates significant efficacy in suppressing laser-induced CNV in mice.
- Suppression of VEGF164 mRNA upregulation appears to be a key mechanism of action.
- YM-344031 holds promise as a potential therapeutic agent for AMD and related neovascular eye diseases.
