PURPOSE: The purpose of this study was to identify the genes, biochemical signaling pathways, and biological themes involved in the pathogenesis of retinopathy of prematurity (ROP). METHODS: Next-generation sequencing (NGS) was performed on the RNA transcriptome of rats with the Penn et al. (Pediatr Res 36:724-731, 1994) oxygen-induced retinopathy model of ROP at the height of vascular abnormality, postnatal day (P) 19, and normalized to age-matched, room-air-reared littermate controls. Eight custom-developed pathways with potential relevance to known ROP sequelae were evaluated for significant regulation in ROP: The three major Wnt signaling pathways, canonical, planar cell polarity (PCP), and Wnt/Ca(2+); two signaling pathways mediated by the Rho GTPases RhoA and Cdc42, which are, respectively, thought to intersect with canonical and non-canonical Wnt signaling; nitric oxide signaling pathways mediated by two nitric oxide synthase (NOS) enzymes, neuronal (nNOS) and endothelial (eNOS); and the retinoic acid (RA) signaling pathway. Regulation of other biological pathways and themes was detected by gene ontology using the Kyoto Encyclopedia of Genes and Genomes and the NIH's Database for Annotation, Visualization, and Integrated Discovery's GO terms databases. RESULTS: Canonical Wnt signaling was found to be regulated, but the non-canonical PCP and Wnt/Ca(2+) pathways were not. Nitric oxide signaling, as measured by the activation of nNOS and eNOS, was also regulated, as was RA signaling. Biological themes related to protein translation (ribosomes), neural signaling, inflammation and immunity, cell cycle, and cell death were (among others) highly regulated in ROP rats. CONCLUSIONS: These several genes and pathways identified by NGS might provide novel targets for intervention in ROP.
PURPOSE: The purpose of this study was to identify the genes, biochemical signaling pathways, and biological themes involved in the pathogenesis of retinopathy of prematurity (ROP). METHODS: Next-generation sequencing (NGS) was performed on the RNA transcriptome of rats with the Penn et al. (Pediatr Res 36:724-731, 1994) oxygen-induced retinopathy model of ROP at the height of vascular abnormality, postnatal day (P) 19, and normalized to age-matched, room-air-reared littermate controls. Eight custom-developed pathways with potential relevance to known ROP sequelae were evaluated for significant regulation in ROP: The three major Wnt signaling pathways, canonical, planar cell polarity (PCP), and Wnt/Ca(2+); two signaling pathways mediated by the Rho GTPases RhoA and Cdc42, which are, respectively, thought to intersect with canonical and non-canonical Wnt signaling; nitric oxide signaling pathways mediated by two nitric oxide synthase (NOS) enzymes, neuronal (nNOS) and endothelial (eNOS); and the retinoic acid (RA) signaling pathway. Regulation of other biological pathways and themes was detected by gene ontology using the Kyoto Encyclopedia of Genes and Genomes and the NIH's Database for Annotation, Visualization, and Integrated Discovery's GO terms databases. RESULTS: Canonical Wnt signaling was found to be regulated, but the non-canonical PCP and Wnt/Ca(2+) pathways were not. Nitric oxide signaling, as measured by the activation of nNOS and eNOS, was also regulated, as was RA signaling. Biological themes related to protein translation (ribosomes), neural signaling, inflammation and immunity, cell cycle, and cell death were (among others) highly regulated in ROP rats. CONCLUSIONS: These several genes and pathways identified by NGS might provide novel targets for intervention in ROP.
Authors: James D Akula; Ronald M Hansen; Radouil Tzekov; Tara L Favazza; Tanya C Vyhovsky; Ilan Y Benador; Julie A Mocko; David McGee; Ryo Kubota; Anne B Fulton Journal: Exp Eye Res Date: 2010-04-27 Impact factor: 3.467
Authors: Xilong Li; Fuller W Bazer; Haijun Gao; Wenjuan Jobgen; Gregory A Johnson; Peng Li; Jason R McKnight; M Carey Satterfield; Thomas E Spencer; Guoyao Wu Journal: Amino Acids Date: 2009-03-06 Impact factor: 3.520
Authors: Nan Zhang; Tara L Favazza; Anna Maria Baglieri; Ilan Y Benador; Emily R Noonan; Anne B Fulton; Ronald M Hansen; P Michael Iuvone; James D Akula Journal: Invest Ophthalmol Vis Sci Date: 2013-12-19 Impact factor: 4.799