Abstract
Background
Retinal gene expression pattern is severely altered after exposition to hyperoxia in mice with oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity. Gene ontology and signaling pathway analyses may add new insights into a better understanding of the pathogenesis of this disease.
Methods
Seven-day-old C57BL/6J mice (n = 60) were exposed to 75% oxygen for 5 days and then recovered in room air. The controls (n = 60) were kept in the normoxic conditions. Retinas were harvested immediately following hyperoxia, during the phase of maximal neovascularization, and at the time of neovascularization regression. The retinal RNA samples were evaluated for gene expression using mouse gene expression microarrays. DAVID annotation tools were used for gene ontology and pathway analyses.
Results
The most significantly enriched signaling pathways during the neovascularization phase of OIR were: focal adhesion; ECM–receptor interaction; PI3K-Akt; oxidative phosphorylation; and Alzheimer’s, Parkinson’s and Huntington’s disease signaling pathways. Genes involved in apoptosis, cell proliferation, cell differentiation, and immune responses were associated with neovascularization regression.
Conclusions
Performed analyses revealed the possible involvement of various signaling pathways in OIR pathomechanism, mostly specific to the OIR phase. Dysregulation of genes involved in oxidative phosphorylation may have an impact on neovascularization development.
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Acknowledgements
We thank Monika Atneossen-Asseng and Grethe Dyrhaug for technical assistance and Agate Noer and Wojciech Zasada for cooperation during procurement of the retina pictures. This work was supported by Polish-Norwegian Research Programme, operated by the National Centre for Research and Development under the Norwegian Financial mechanism 2009-2014 in the frame of Project Contract No. Pol-Nor/196065/54/2013.
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Substantial contributions to conception and design—M.Z., C.R., A.M.-T., A.G.W.R., O.D.S., M.B.-M., J.J.P., P.K.; acquisition of data—M.Z., A.M.-T., C.R., A.G.W.R., T.K., K.S., A.G.; analysis and interpretation of data—A.M.-T., M.Z.; drafting the article or revising it critically for important intellectual content—M.Z., A.M.-T., C.R., L.O.B., O.D.S., M.B.-M., J.J.P., P.K.; final approval of the version to be published—all authors.
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Zasada, M., Madetko-Talowska, A., Revhaug, C. et al. Transcriptome analysis reveals dysregulation of genes involved in oxidative phosphorylation in a murine model of retinopathy of prematurity. Pediatr Res 88, 391–397 (2020). https://doi.org/10.1038/s41390-020-0793-x
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DOI: https://doi.org/10.1038/s41390-020-0793-x
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