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Neuropilin-1 high monocytes protect against neonatal inflammation

ABSTRACT: Neuropilin-1 high monocytes protect against neonatal inflammation

PROVIDER: PRJNA1097663 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28591918_1.fastq.gz	Fastqsanger.gz
	SRR28591918_2.fastq.gz	Fastqsanger.gz
	SRR28591919_1.fastq.gz	Fastqsanger.gz
	SRR28591919_2.fastq.gz	Fastqsanger.gz
	SRR28591920_1.fastq.gz	Fastqsanger.gz

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Project description:Introduction: Retinopathy of prematurity (ROP) with early vessel loss (Phase I) followed by uncontrolled vessel growth (Phase II) causes visual impairment in premature infants. Although supplementation with n-3 docosahexaenoic acid (DHA) alone has mixed results to prevent ROP, combined supplementation with DHA and n-6 arachidonic acid (ARA) in early postnatal life reduces severe ROP by 50% (Mega Donna Mega study). The underlying mechanisms are unknown. Objectives: To evaluate protective effects and mechanism of combined dietary n-3 DHA and n-6 ARA in a neonatal mouse model of Phase I ROP. Methods: In the Mega Donna Mega study, most preterm infants had early postnatal hyperglycemia episodes, a strong risk factor for severe ROP. We used a neonatal mouse model of hyperglycemia-induced suppression of retinal vascular development (Phase I ROP). Dams were fed diets enriched with 3%DHA or 1%DHA+2%ARA. In P10 milk-fed pups, we assessed retinal vascularization, and proteome, and fatty acid profiles in retina, retinal pigment epithelium (RPE) complex and plasma. In vivo, oligomycin A, a mitochondrial ATP synthase inhibitor, was used to assess mitochondrial participation in the combined lipid protective effects. Results: In 201 (97.6%) of 206 randomized infants there was at least one elevated glucose measurement during the first 14 days. In a neonatal mouse model of hyperglycemia-induced suppression of vascular development, maternal DHA+ARA vs. DHA diet promoted pup retinal vessel growth. Fatty acid profiling confirmed lipid changes in pup plasma and RPE complex in accord with DHA and ARA levels in the maternal diets. Proteomic retinal analysis revealed increased abundance of proteins related to mitochondrial respiration and glucose metabolism in the combined diet. Inhibition of mitochondrial ATP synthase negated the protective effects of the combined diet on retinal vascularization. Conclusion: Combined DHA+ARA oral supplementation in the early postnatal period protects against Phase I ROP in mouse neonates, through enhanced retinal metabolism suggesting the potential of balanced lipid supplementation for preventing ROP.

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Neuropilin-1 high monocytes protect against neonatal inflammation

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