Citation:Yuan LH,Chen XL,Di Y,Liu ML.CCR7/p-ERK1/2/VEGF signaling promotes retinal neovascularization in a mouse model of oxygen-induced retinopathy.Int J Ophthalmol 2017;10(6):862-869,doi:10.18240/ijo.2017.06.06
CCR7/p-ERK1/2/VEGF signaling promotes retinal neovascularization in a mouse model of oxygen-induced retinopathy
Received:October 24, 2016  Revised:February 14, 2017
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DOI:10.18240/ijo.2017.06.06
Key Words:chemokine receptor type 7  vascular endothelial growth factor  extracellular signal-regulated kinase  retinal neovascularization  retinopathy of prematurity
Fund Project:Supported by the Science and Technology Planning Foundation of Liaoning Province (No.2010225034).
           
AuthorInstitution
Lin-Hui Yuan Department of Ophthalmology, Shengjing Affiliated Hospital of China Medical University, Shenyang , Liaoning Province, China
Xiao-Long Chen Department of Ophthalmology, Shengjing Affiliated Hospital of China Medical University, Shenyang , Liaoning Province, China
Yu Di Department of Ophthalmology, Shengjing Affiliated Hospital of China Medical University, Shenyang , Liaoning Province, China
Mei-Lin Liu Department of Ophthalmology, Shengjing Affiliated Hospital of China Medical University, Shenyang , Liaoning Province, China
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Abstract:
      AIM: To investigate the role of CCR7/p-ERK1/2/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-ERK1/2 and vascular 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-ERK1/2, and VEGF expression in the OIR mouse model (all P<0.05). CCR7 significantly enhanced the 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 1/2/VEGF signaling plays an important role in OIR. CCR7 may be a potential target for the prevention and treatment of retinopathy of prematurity.

PMC FullText Html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515149/
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