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T. Sato, S. Kusaka, N. Hashida, Y. Saishin, T. Fujikado, Y. Tano; Comprehensive Gene Expression Profiles in Murine Oxygen-induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2626.
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To investigate a comprehensive expression profile of genes in murine oxygen-induced retinopathy (OIR), and to correlate the expression pattern of the genes with the clinical time course of OIR.
OIR was induced in C57BL/6 mice by placing postnatal day 7 (P7) pups in 75% oxygen for 5 days. The time course of OIR was evaluated daily on retinal flat-mounts from P12 to P21. Microarray analysis was performed on OIR and control retinas on P17 to select the candidates for TaqMan® low-density array (TLDA). Real-time PCR with TLDA was performed by comparative CT method at P12 to P21, and the successive expression patterns of the genes in OIR were analyzed by hierarchical clustering.
Microarray analysis showed that 25 probes associated with angiogenesis were up-regulated and 3 probes were down-regulated in murine OIR. TLDA cluster analysis revealed a homology of gene expression patterns between P12 and P13 and between P16 and P17. Many genes associated with inflammation were up-regulated from the beginning when the degrees of both central avascular area and central vasoconstriction were maximal, and the up-regulation of the genes continued to the late stage. Several genes associated with angiogenesis, such as angiopoietin-2 and vascular endothelial growth factor-A, were remarkably up-regulated around P16 and P17 when extraretinal neovascularization became most noticeable.
An increase in the expression of genes associated with inflammation preceded the angiogenesis and the up-regulation of genes associated with angiogenesis. The gene expression patterns were well-correlated with the clinical presentations. These findings will be valuable for the understanding of the pathological conditions involved in angiogenesis.
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