AIM： To investigate the role of CCR7/p-ERKI/2/VEGF signaling in the mouse model of oxygen-induced retinopathy （OIR）. METHODS： Neonatal C57BL/6J mice were evenly randomized into four groups： normoxia, OIR, OIR co...AIM： To investigate the role of CCR7/p-ERKI/2/VEGF signaling in the mouse model of oxygen-induced retinopathy （OIR）. METHODS： Neonatal C57BL/6J mice were evenly randomized into four groups： normoxia, OIR, OIR control （treated with scramble siRNA）, and OIR treated （treated with CCR7 siRNA）. Normoxia group was not specially handled. Postnatal day 7 （P7） mice in the OIR group were exposed to 75%±5% oxygen for 5d （P7-P12） and then maintained under normoxic conditions for 5d （P12-P17）. Mice in the OIR control and OIR treated groups were given injections of scramble or CCR7 siRNA plasmid on P12 before returning to normoxic conditions for 5d （P12-P17）. Retina samples were collected from all mice on P17, stained with adenosine diphosphatase （ADPase）, and retinal neovascularization （RNV） was assessed. Retinas were also stained with hematoxylin and eosin （H＆E） for RNV quantitation. The distribution and expression of CCR7, p-ERKI/2 and vas- cular endothelial growth factor （VEGF） were assessed via immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR）. RESULTS： High oxygen promoted retinal neovascularization （P〈0.05） and increased the number of endothelial nuclei in new vessels extending from the retina to the vitreous body; CCR7 promoted this process （P〈0.05）. CCR7 and VEGF mRNA were expressed at higher levels in the OIR and OIR control groups than in the normoxia and OIR treated groups. CCR7, p-ERK1/2, and VEGF protein were expressed in the retinas of mice in the OIR and OIR control groups. Intravitreal injection of CCR7 siRNA significantly reduced CCR7, p-ERKI/2, and VEGF expression in the OIR mouse model （all P〈0.05）. CCR7 significantly enhancedthe neovascularization and non-perfusion areas in the OIR group （P〈0,05）, CCR7 siRNA significantly reduced levels of p-ERK1/2 and VEGF as compared to OIR controls （P〈0.05）. CONCLUSION： These results suggest that CCR7/p-ERK I/2NEGF signaling plays an important role in OIR, CCR7 may be a potential target for the prevention and treatment of retinopathy of prematurity.展开更多
基金Supported by the Science and Technology Planning Foundation of Liaoning Province(No.2010225034)
文摘AIM： To investigate the role of CCR7/p-ERKI/2/VEGF signaling in the mouse model of oxygen-induced retinopathy （OIR）. METHODS： Neonatal C57BL/6J mice were evenly randomized into four groups： normoxia, OIR, OIR control （treated with scramble siRNA）, and OIR treated （treated with CCR7 siRNA）. Normoxia group was not specially handled. Postnatal day 7 （P7） mice in the OIR group were exposed to 75%±5% oxygen for 5d （P7-P12） and then maintained under normoxic conditions for 5d （P12-P17）. Mice in the OIR control and OIR treated groups were given injections of scramble or CCR7 siRNA plasmid on P12 before returning to normoxic conditions for 5d （P12-P17）. Retina samples were collected from all mice on P17, stained with adenosine diphosphatase （ADPase）, and retinal neovascularization （RNV） was assessed. Retinas were also stained with hematoxylin and eosin （H＆E） for RNV quantitation. The distribution and expression of CCR7, p-ERKI/2 and vas- cular endothelial growth factor （VEGF） were assessed via immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR）. RESULTS： High oxygen promoted retinal neovascularization （P〈0.05） and increased the number of endothelial nuclei in new vessels extending from the retina to the vitreous body; CCR7 promoted this process （P〈0.05）. CCR7 and VEGF mRNA were expressed at higher levels in the OIR and OIR control groups than in the normoxia and OIR treated groups. CCR7, p-ERK1/2, and VEGF protein were expressed in the retinas of mice in the OIR and OIR control groups. Intravitreal injection of CCR7 siRNA significantly reduced CCR7, p-ERKI/2, and VEGF expression in the OIR mouse model （all P〈0.05）. CCR7 significantly enhancedthe neovascularization and non-perfusion areas in the OIR group （P〈0,05）, CCR7 siRNA significantly reduced levels of p-ERK1/2 and VEGF as compared to OIR controls （P〈0.05）. CONCLUSION： These results suggest that CCR7/p-ERK I/2NEGF signaling plays an important role in OIR, CCR7 may be a potential target for the prevention and treatment of retinopathy of prematurity.
