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Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity

ABSTRACT: Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity

PROVIDER: PRJNA901967 | ENA |

REPOSITORIES: ENA

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Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity

Project description:Retinopathy of prematurity (ROP), a blinding condition affecting preterm infants, accounts for up to 40% of all childhood blindness worldwide. ROP is an interruption of retinal vascular maturation, which is physiologically complete at full term and thus ongoing at the time of preterm birth. Although ROP demonstrates delayed onset following preterm birth, representing a window for therapeutic intervention, we cannot cure or prevent this disease. The in-utero environment, including placental function, is increasingly recognized for contributions to preterm infant disease risk. Herein, we examine the clinical associations between presence and severity of acute placental inflammation to ROP risk. Using logistic regression, we find a protective relationship between presence and severity of acute placental inflammation and preterm infant development of ROP. This is most significant for infants born in the absence of maternal preeclampsia. Further, we examine the underlying molecular mediators that may inform this protective paradigm. Adopting a candidate approach analyzing proteins with described ROP risk associations, we find that placental HTRA1 and FABP4 protein expression is significantly decreased within placental tissues characterized by acute inflammation. Additionally, HTRA1 and VEGFA demonstrate inverse longitudinal trends within the peripheral circulation for infants born in the presence compared to absence of acute placental inflammation. An agnostic approach, including whole transcriptome and differential methylation placental analysis, identifies novel mediators and pathways that may underly protection. Taken together, these data build on emerging literature showing disparate associations between acute placental inflammation and ROP development within preeclamptic or non-preeclamptic preterm infant populations and identifies novel placental mechanisms that may inform postnatal risk associations in preterm infants.

2023-01-01 | GSE218039 | GEO

Circular RNA Profiling in Peripheral Blood Mononuclear Cells from Retinopathy of Prematurity

Project description:To reveal the altered expression profiles of circular RNAs (circRNAs) in the peripheral blood mononuclear cells (PBMCs) of patients with retinopathy of prematurity (ROP), microarray analysis was conducted in the samples from ROP patients and controls.

2022-08-10 | GSE204780 | GEO

Epithelial membrane protein-2 promotes VEGF signaling to promote pathological neovascular growth in retinopathy of prematurity

Project description:Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, and exclusively affects infants born prematurely. In this study, we test the hypothesis that EMP2 contributes to neovascularization in a mouse model of the disease. We show that EMP2 promotes neuronal VEGF signaling and that its downregulation reduces severity of neovascularization.

2021-12-17 | GSE123945 | GEO

Clinical and Genetic Analysis of Retinopathy of Prematurity-GWAS

Project description:Clinical and Genetic Analysis of Retinopathy of Prematurity-GWAS

| PRJNA627780 | ENA

Clinical and Genetic Analysis of Retinopathy of Prematurity-GWAS

Project description:Clinical and Genetic Analysis of Retinopathy of Prematurity-GWAS

| PRJNA627779 | ENA

Clinical and Genetic (Whole Exome Sequences) Analysis of Retinopathy of Prematurity

Project description:Clinical and Genetic (Whole Exome Sequences) Analysis of Retinopathy of Prematurity

| PRJNA638975 | ENA

Clinical and Genetic (Whole Exome Sequences) Analysis of Retinopathy of Prematurity

Project description:Clinical and Genetic (Whole Exome Sequences) Analysis of Retinopathy of Prematurity

| PRJNA638974 | ENA

Circular RNA Profiling in Peripheral Blood Mononuclear Cells from Retinopathy of Prematurity

Project description:Circular RNA Profiling in Peripheral Blood Mononuclear Cells from Retinopathy of Prematurity

| PRJNA842269 | ENA

Gene expression microarray analysis of early oxygen-induced retinopathy (OIR)

Project description:Different inbred strains of rats differ in their susceptibility to OIR, an animal model of human retinopathy of prematurity. We examined gene expression profiles in Fischer 344 (F344, resistant to OIR) and Sprague Dawley (SD, susceptible to OIR) rats at the early time point of day 3 to identifying gene pathways related to the underlying genetic cause of phenotypic differences between strains.

2009-11-13 | GSE18998 | GEO

Serine and 1-carbon metabolism are required for HIF-mediated protection against retinopathy of prematurity

Project description:We determined which metabolic pathways are activated by hypoxia-inducible factor 1-mediated (HIF-1-mediated) protection against oxygen-induced retinopathy (OIR) in newborn mice, the experimental correlate to retinopathy of prematurity, a leading cause of infant blindness. HIF-1 coordinates the change from oxidative to glycolytic metabolism and mediates flux through serine and 1-carbon metabolism (1CM) in hypoxic and cancer cells. We used untargeted metabolite profiling in vivo to demonstrate that hypoxia mimesis activates serine/1CM. Both [13C6] glucose labeling of metabolites in ex vivo retinal explants as well as in vivo [13C3] serine labeling of metabolites followed in liver lysates strongly suggest that retinal serine is primarily derived from hepatic glycolytic carbon and not from retinal glycolytic carbon in newborn pups. In HIF-1α2lox/2lox albumin-Cre-knockout mice, reduced or near-0 levels of serine/glycine further demonstrate the hepatic origin of retinal serine. Furthermore, inhibition of 1CM by methotrexate blocked HIF-mediated protection against OIR. This demonstrated that 1CM participates in protection induced by HIF-1 stabilization. The urea cycle also dominated pathway enrichment analyses of plasma samples. The dependence of retinal serine on hepatic HIF-1 and the upregulation of the urea cycle emphasize the importance of the liver to remote protection of the retina.

2019-07-05 | MTBLS856 | MetaboLights

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