TY - JOUR
T1 - Next-generation sequencing analysis of gene regulation in the rat model of retinopathy of prematurity
AU - Griffith, Rachel M.
AU - Li, Hu
AU - Zhang, Nan
AU - Favazza, Tara L.
AU - Fulton, Anne B.
AU - Hansen, Ronald M.
AU - Akula, James D.
N1 - Funding Information:
Acknowledgments This work was supported by NIH EY020308 (JDA) and the Massachusetts Lions Eye Research Fund (RMH).
PY - 2013/8
Y1 - 2013/8
N2 - 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/Ca2+; 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/Ca2+ 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.
AB - 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/Ca2+; 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/Ca2+ 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.
KW - Next-generation sequencing
KW - Nitric oxide
KW - Retinoic acid
KW - Retinopathy of prematurity
KW - Rho GTPase
KW - Wnt signaling
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U2 - 10.1007/s10633-013-9396-8
DO - 10.1007/s10633-013-9396-8
M3 - Article
C2 - 23775346
AN - SCOPUS:84882238662
SN - 0012-4486
VL - 127
SP - 13
EP - 31
JO - Documenta Ophthalmologica
JF - Documenta Ophthalmologica
IS - 1
ER -