Omega 3, 6 long-chain fatty acid imbalance delays neurovascular development in hyperglycemia-associated retinopathy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA816874 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18338322.fastq.gz | Fastqsanger.gz | |||
| SRR18338323.fastq.gz | Fastqsanger.gz | |||
| SRR18338324.fastq.gz | Fastqsanger.gz | |||
| SRR18338325.fastq.gz | Fastqsanger.gz | |||
| SRR18338326.fastq.gz | Fastqsanger.gz |
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Project description:There is a gap in our understanding of the protective effect of the essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) on proliferative retinopathies. In retinopathy of prematurity (ROP), DHA supplementation alone may not reduce the risk for severe disease. We found that in mouse neonates with hyperglycemia-associated retinopathy (HAR) with impaired retinal vessel growth modeling Phase I ROP versus controls, there was a strong metabolic shift in almost all types of retinal neuronal cells identified with single-cell transcriptomics. Loss of adiponectin (Apn-/-), modeling low APN seen in premature infants, caused a ω-3 and ω-6 LCPUFA imbalance in HAR mouse retinas. Dietary intake of ω-3 vs ω-6 LCPUFA promoted retinal vessel growth, associated with increased APN levels and increased retinal APN receptor AdipoR1 gene expression. Interestingly, we found that ω-6 vs. ω-3 LCPUFA was essential in maintaining retinal metabolism and neuronal development. Our findings suggest that both ω-3 and ω-6 LCPUFA are essential in protecting against retinal neurovascular dysfunction in Phase I ROP model. Maintaining adequate ω-6 LCPUFA levels is required while supplementing ω-3 LCPUFA to prevent retinopathy.
2022-04-20 | GSE198785 | GEO
Project description:Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic β-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina. Intravitreal (5ug or 10ug) or subcutaneous (30mg/kg) injection of STZ at the early stage of newborn rats couldn’t induce hyperglycemia but caused NSIR (neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn’t induce NSIR when all retinal progenitors exit the cell cycle. Thus, NSIR in rats is independent of hyperglycemia but due to STZ’s direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.
2024-07-16 | GSE272311 | GEO
Project description:There is a gap in understanding the effect of the essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy of prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to Phase I ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated Phase I retinopathy, dietary ω-3 (vs. ω-6 LCPUFA) supplementation promoted retinal vessel development. However, ω-6 (vs. ω-3 LCPUFA) was also developmentally essential, promoting neuronal growth and metabolism as suggested by a strong metabolic shift in almost all types of retinal neuronal and glial cells identified with single-cell transcriptomics. Loss of adiponectin (APN) in mice (mimicking the low APN levels in Phase I ROP) decreased LCPUFA levels (including ω-3 and ω-6) in retinas under normoglycemic and hyperglycemic conditions. ω-3 (vs. ω-6) LCPUFA activated the APN pathway by increasing the circulating APN levels and inducing expression of the retinal APN receptor. Our findings suggested that both ω-3 and ω-6 LCPUFA are crucial in protecting against retinal neurovascular dysfunction in a Phase I ROP model; adequate ω-6 LCPUFA levels must be maintained in addition to ω-3 supplementation to prevent retinopathy. Activation of the APN pathway may further enhance the ω-3 and ω-6 LCPUFA's protection against ROP.
| S-EPMC9002570 | biostudies-literature
Project description:Hyperglycemia-independent neonatal streptozotocin-induced retinopathy (NSIR) in rats
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Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.
2016-03-15 | E-GEOD-72123 | biostudies-arrayexpress
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status.
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Project description:This study explored how the omega-6 to omega-3 fatty acid ratio in low-fish oil aquafeeds influences Atlantic salmon's antiviral and antibacterial immune responses. Atlantic salmon were fed aquafeeds rich in soy oil (high in omega-6) or linseed oil (high in omega-3) for 12 weeks and then challenged with bacterial (formalin-killed Aeromonas salmonicida; Asal) or viral-like (polyriboinosinic polyribocytidylic acid; pIC) antigens. The mRNA levels of 46 immune-relevant genes in the head kidneys of the salmon were analyzed via quantitative real-time polymerase chain reaction (RT-qPCR).
2024-05-13 | GSE249779 | GEO
Project description:The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer’s disease (AD). Therefore, effective drugs against AD should be able to target the multi-cellular neurovascular unit and the therapeutic relationships among neurovascular cells should be defined. We aimed to examine the therapeutic effects of an herbal remedy with multi-targeting capabilities, ukgansan (UGS), using in vitro models of AD, and to assess the similarity among neurovascular cells in terms of a therapeutic network.
2019-07-18 | GSE134414 | GEO
Project description:Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) have important signalling roles in the hypothalamus, a region of the brain that regulates whole-body energy homeostasis. While evidence suggests that high PUFA intake can impact hypothalamic activity, the underlying molecular mechanisms regulated by essential dietary PUFA (i.e., linoleic acid and alpha-linolenic acid) remain poorly described in this brain region. To differentiate the roles of essential dietary PUFA on hypothalamic function, we fed male rats high-fat diets (35% kcal/d) containing either safflower (linoleic acid) or flaxseed (alpha-linolenic acid) oil for 2 months. Control rats were fed a low-fat (16% kcal/d) diet containing soybean oil. Hypothalmic gene expression was investigated by microrray.
2018-08-29 | GSE104338 | GEO
Project description:Cyclonatronum proteinivorum strain:Omega Genome sequencing and assembly
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