Background To investigate the underlying mechanism of S100A4 function and whether it has a role in retinal neovascularization (RNV) in a mouse model of oxygen-induced retinopathy (OIR). Methods Retinas from a mouse model of OIR were treated with and without an intravitreous injection of adenoviral-S100A4-RNAi or adenoviral green fluorescence protein (GFP) at postnatal day 12 (P12). At P17, the efficacy of adenoviral gene transfer was assessed using fluorescence microscopy and western blot analysis. RNV was evaluated by wholemount immunofluorescence staining of the mouse retina and by counting the number of pre-retinal neovascular cells. Protein and mRNA expression levels of S100A4, brainderived growth factor (BDNF), and vascular endothelial growth factor (VEGF) were measured using western blot analysis and real-time PCR. Results Retinal S100A4 levels were positively correlated with the progression of RNV. In the OIR-S100A4-RNAi group, both protein and mRNA expression levels of S100A4 in the retina significantly decreased at P17 compared with those in the OIR group. Ad-S100A4-RNAi transfer was clearly demonstrated by GFP fluorescence in many layers of the retina 5 days after the Ad-S100A4-RNAi transfer. Whole-mount immunofluorescence staining of the retina and quantification of the pre-retinal neovascular cells demonstrated that RNV was significantly inhibited. Meanwhile, the levels of the transcription and translation of BDNF,
Our results indicated that RNV was ameliorated by Ad-S100A4-RNAi transfer in a mouse model of OIR through mediation of the anti-apoptotic effect of Bcl-2 by reducing the expression of CREB, and that S100A4 may be a novel therapeutic target for ocular neovascularization diseases.
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