Comprehensive gene-expression profile in murine oxygen-induced retinopathy.

Abstract

To investigate the correlation between the clinical course and gene-expression pattern in murine oxygen-induced retinopathy (OIR), a commonly used model of retinopathy of prematurity (ROP). OIR was induced in C57BL/6N mice by placing postnatal day 7 (P7) pups in 75% oxygen for 5 days. The clinical course of the OIR was evaluated on retinal flat-mounts after fluorescein isothiocyanate-conjugated dextran perfusion from P12 to P21. The expression values of 94 genes, selected by microarray analyses, were determined daily from P12 through P21 by RT-PCR with TaqMan low-density array (TLDA) and analysed by hierarchical clustering. TLDA cluster analyses showed a homology of gene-expression pattern between P12 and P13 and between P16 and P17. Many genes associated with inflammation were upregulated on P12 and P13 when the degree of both central avascular area and central vasoconstriction were maximal, and the upregulation of the genes continued to P21. At P16 and P17 when extraretinal neovascularisation became most noticeable, several genes associated with angiogenesis, for example, vascular endothelial growth factor-A and angiopoietin-2, were most upregulated. The gene-expression pattern was well correlated with the clinical appearance in murine OIR. These findings should contribute to the understanding of the pathological conditions in ROP.