Gene Expression Changes in a Rat Model of Oxygen-Induced Retinopathy

Lee, Na Eun; Park, Yeon Jeong; Chung, In‐Young; Seo, Seong Wook; Park, Jong; Yoo, Ji Myung; Song, Jinnan

doi:10.3341/kjo.2011.25.1.42

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…Accumulating evidence has demonstrated that NFATc4 exerts a proapoptotic effect in multiple diseases, and might participate in retinal ganglion cell apoptosis [ 100 ]. The proteoglycan decorin, encoded by the Dcn gene from the group, may also play a role in the differentiation of retinal ganglion cells [ 101 ] and is involved in hypoxic retinal damage, significantly reduce in expression in oxygen-induced retinopathy [ 102 , 103 ].…”

Section: Discussionmentioning

confidence: 99%

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

et al. 2014

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BackgroundEtiology of complex disorders, such as cataract and neurodegenerative diseases including age-related macular degeneration (AMD), remains poorly understood due to the paucity of animal models, fully replicating the human disease. Previously, two quantitative trait loci (QTLs) associated with early cataract, AMD-like retinopathy, and some behavioral aberrations in senescence-accelerated OXYS rats were uncovered on chromosome 1 in a cross between OXYS and WAG rats. To confirm the findings, we generated interval-specific congenic strains, WAG/OXYS-1.1 and WAG/OXYS-1.2, carrying OXYS-derived loci of chromosome 1 in the WAG strain. Both congenic strains displayed early cataract and retinopathy but differed clinically from OXYS rats. Here we applied a high-throughput RNA sequencing (RNA-Seq) strategy to facilitate nomination of the candidate genes and functional pathways that may be responsible for these differences and can contribute to the development of the senescence-accelerated phenotype of OXYS rats.ResultsFirst, the size and map position of QTL-derived congenic segments were determined by comparative analysis of coding single-nucleotide polymorphisms (SNPs), which were identified for OXYS, WAG, and congenic retinal RNAs after sequencing. The transferred locus was not what we expected in WAG/OXYS-1.1 rats. In rat retina, 15442 genes were expressed. Coherent sets of differentially expressed genes were identified when we compared RNA-Seq retinal profiles of 20-day-old WAG/OXYS-1.1, WAG/OXYS-1.2, and OXYS rats. The genes most different in the average expression level between the congenic strains included those generally associated with the Wnt, integrin, and TGF-β signaling pathways, widely involved in neurodegenerative processes. Several candidate genes (including Arhgap33, Cebpg, Gtf3c1, Snurf, Tnfaip3, Yme1l1, Cbs, Car9 and Fn1) were found to be either polymorphic in the congenic loci or differentially expressed between the strains. These genes may contribute to the development of cataract and retinopathy.ConclusionsThis study is the first RNA-Seq analysis of the rat retinal transcriptome generated with 40 mln sequencing read depth. The integration of QTL and transcriptomic analyses in our study forms the basis of future research into the relationship between the candidate genes within the congenic regions and specific changes in the retinal transcriptome as possible causal mechanisms that underlie age-associated disorders.

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Section: Discussionmentioning

confidence: 99%

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

et al. 2014

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“…Although several papers have employed gene chips to analyze expression in murine OIR models of ROP [144-147], only one (to our knowledge), Recchia et al [40], did so in the 50/10 ROP rat. Thus, in our study, genes were deemed ‘regulated’ if the fold change (FC) was greater than 1.7, up (+0.77 log 2 ) or down (-0.77 log 2 ), for easy comparison to Recchia et al 's gene chip results wherein this was the cutoff used for significance.…”

Section: Methodsmentioning

confidence: 99%

Next-generation sequencing analysis of gene regulation in the rat model of retinopathy of prematurity

Griffith

Zhang

et al. 2013

Doc Ophthalmol

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Purpose 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. (1994) oxygen-induced retinopathy (OIR) 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 noncanonical Wnt signaling, nitric oxide signaling pathways mediated by two nitrox oxide synthase (NOS) enzymes, neuronal (nNOS) and endothelial (eNOS), and the retinoic acid (RA) signaling pathway. Regulation of other biological pathways and themes were detected by gene ontology using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the NIH's Database for Annotation, Visualization and Integrated Discovery (DAVID)'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 (NO) signaling, as measured by the activation of nNOS 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.

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“…Decrease in decorin levels can reflect cellular damage and cell death whilst the recovery of decorin can occur in response to retinal regenerative processes or be associated with several inflammatory responses. Oxygen induced retinopathy (OIR) in Sprague–Dawley rats displayed significant decrease in decorin expression as compared to their controls [ 42 ]. Another study also found similar results whereby OIR rats with severe retinal injury and neuronal cell death presented significantly reduced decorin mRNA and protein expression [ 43 ].…”

Section: Class I Retinal Slrpsmentioning

confidence: 99%

Small Leucine-Rich Proteoglycans (SLRPs) in the Retina

Low

Connor

Kassem

et al. 2021

IJMS

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Retinal diseases such as age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and diabetic retinopathy (DR) are the leading causes of visual impairment worldwide. There is a critical need to understand the structural and cellular components that play a vital role in the pathophysiology of retinal diseases. One potential component is the family of structural proteins called small leucine-rich proteoglycans (SLRPs). SLRPs are crucial in many fundamental biological processes involved in the maintenance of retinal homeostasis. They are present within the extracellular matrix (ECM) of connective and vascular tissues and contribute to tissue organization and modulation of cell growth. They play a vital role in cell–matrix interactions in many upstream signaling pathways involved in fibrillogenesis and angiogenesis. In this comprehensive review, we describe the expression patterns and function of SLRPs in the retina, including Biglycan and Decorin from class I; Fibromodulin, Lumican, and a Proline/arginine-rich end leucine-rich repeat protein (PRELP) from class II; Opticin and Osteoglycin/Mimecan from class III; and Chondroadherin (CHAD), Tsukushi and Nyctalopin from class IV.

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Gene Expression Changes in a Rat Model of Oxygen-Induced Retinopathy

Cited by 4 publications

References 16 publications

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

Next-generation sequencing analysis of gene regulation in the rat model of retinopathy of prematurity

Small Leucine-Rich Proteoglycans (SLRPs) in the Retina

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