Abstract
Purpose: :
Recent study showed that the chemokine receptor CCR3 is specifically expressed in choroidal neovascularization (CNV) of age-related macular degeneration (AMD), and CCR3 inhibition suppress CNV (Takeda A et al, Nature, 2009). The purpose of this study is to evaluate the efficacy of CCR3 antagonist on laser injury-induced CNV in mice.
Methods: :
We employed YM-344031, a novel and selective small molecule CCR3 antagonist potently inhibited the ligand binding. CNV was induced by laser injury in C57BL/6J mice, and volumes measured 7 days later by confocal evaluation of Griffonia simplicifolia Isolectin B4 staining of RPE-choroid flatmounts. Leakage from the CNV was also measured by fluorescein angiography 7 days after laser treatment.CCR3 antagonist, 50mg/kg/day of YM-344031 or same volume of vehicle (DMSO) was given by gavage to mice 1 hour before laser and 1 day after laser. For topical administration of CCR3 antagonist, YM-344031, dissolved in vehicle (DMSO) (0.1-10µg) were injected into the vitreous humor using a 33-gauge needle immediately after laser injury.
Results: :
CNV volume was significantly suppressed by oral administration of CCR3 antagonist, YM-344031 compared to vehicle (148891.6±27311.9 µm3 , 382762.4±15047.7 µm3 respectively, p<0.0001). Vitreous injection of CCR3 also showed CNV volume suppression in dose-dependent manner. CCR3 antagonist (10µg) showed significant suppression in CNV volume compare to vehicle (193775.6± 19265.9 µm3, 339812.2±43581.9 µm3 respectively, p<0.05).
Conclusions: :
This study reinforces the previous study that CCR3 is involved in CNV development and may consider potential of new therapy for AMD.
Keywords: age-related macular degeneration • choroid: neovascularization • cytokines/chemokines