Inhibitory effect of CXCR4 inhibitor combined with anti-vascular endothelial growth factor antibody on experimental choroidal neovascularization

Abstract

Objective To observe the effects of CXCR4 inhibitor (AMD3100) combined with antivascular endothelial growth factor (VEGF) antibody on experimental choroidal neovascularization.Methods Choroidal neovascularization (CNV) was induced in 48 Brown-Norway (BN) rats by Krypton red laser photocoagulation,and those rats were randomly divided into AF564 group (group A),AMD3100 group (group B),combined treatment group (group C) and PBS group (group D),12 rats in each group.Left eyes were the experimental eyes.The rats of group A - D received intravitreal injection of 5μl of AF564,AMD3100,AF564/AMD3100 and PBS after laser photocoagulation respectively.Fourteen days after photocoagulation,fundus fluorescein angiography (FFA),pathological section analysis and choroidal vascular wholemount were used to observe the degree of fluorescein leakage,the relative thickness and areas of CNV.Results Fourteen days after photocoagulation,the scores of fluorescein leakage in group A - D were 2.16±0.91,2.16±0.91,1.92±1.03,1.39±0.93 respectively.Fluorescein leakage in group A - C was obviously reduced compared to group D (F =12.91,P＜0.001 ),while fluorescein leakage in group C was reduced compared to group A and B (F=9.21,P＜0.05 ).The CNV relative thicknesses in group A-D were 1.82±0.11,1.90±0.22,1.12±0.12,2.82±0.29 respectively.Group A -C had thinner CNV compared to group D (F=5.92,P＜0.001),while group C had thinner CNV compared to group A and B (F=5.16,P＜0.05).The CNV areas in group A - D were (8204± 122),(9332±211),(6533± 101),and (13644±255) μm2 respectively.Group A - C had smaller CNV area compared to group D (F=147.50,P＜0.001),while group C had smaller CNV area compared to group A and B (F=112.60,P＜0.05).Conclusion Combined treatment with CXCR4 inhibitor and anti-VEGF antibody can inhibit laser-induced CNV significantly. Key words: Choroidal neovascularization/therapy; Receptors, CXCR4/ drug effects; Vascular endothelial growth factors; Chemokine CXCL12 ; Disease models, animal