Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: retinopathy of prematurity • retinal neovascularization • gene/expression