Short- and long-term impact of hyperoxia on the blood and retinal cells\u2019 transcriptome in a mouse model of oxygen-induced retinopathy

Magdalena Zasada,Ola Didrik Saugstad,Anna Madetko-Talowska,Agnieszka Grabowska,Jacek Józef Pietrzyk,Katarzyna Szewczyk,Teofila Książek,Miroslaw Bik-Multanowski,Przemko Kwinta,Cecilie Revhaug,Lars O Baumbusch,Anne Gro W Rognlien

doi:10.1038/s41390-019-0598-y

Abstract

BackgroundWe aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers.MethodsA total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays.ResultsThere were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17.ConclusionThere are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.

Highlights

Retinopathy of prematurity (ROP), a proliferative retinal vascular disorder affecting premature infants, is currently a major cause of potentially preventable blindness in children.[1]
487 RESULTS Animal model of oxygen-induced retinopathy (OIR) On postnatal day 7 (P7), 120 C57BL/6J mice underwent the experiment—60 were randomly assigned to the OIR group, and the other 60 formed the control group
There were no significant weight differences between the groups when entering experiment (P7); OIR group revealed transient significant extrauterine growth retardation on P12, which normalized after day P17 (Table 2)

Summary

Introduction

Retinopathy of prematurity (ROP), a proliferative retinal vascular disorder affecting premature infants, is currently a major cause of potentially preventable blindness in children.[1]. The most widely used model is a murine model of oxygen-induced retinopathy (OIR).[5] In mice, the retinas are mostly avascular after birth, and retinal vascularization occurs in the early neonatal period, resembling situation observed in the prematurely born infants. The goal of this study was to identify potential ROP blood biomarkers and provide a more molecular-based understanding of ROP by comparing the gene expression profile at three time points (vaso-obliteration (P12), maximal neovascularization (P17) and during normalization of the retinal damage (P28)) in the blood mononuclear cells and retinas obtained from the mice with and without OIR. We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers. An altered expression of Deptor and Nol[4] genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization

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