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Sökning: WFRF:(Löfqvist J)

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  • Fu, Z. J., et al. (författare)
  • Dietary omega-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin
  • 2015
  • Ingår i: American Journal of Clinical Nutrition. - 0002-9165. ; 101:4, s. 879-888
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary omega-3 (n-3) long-chain polyunsaturated fatty acids (omega-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. Objective: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary omega-3 LCPUFAs to mediate the protective effect in ROP. Design: Serum APN concentrations were correlated with ROP development and serum omega-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether omega-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. Results: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum omega-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by omega-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. omega-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary omega-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. Conclusion: Our findings suggest that increasing APN by omega-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.
  • Connor, K. M., et al. (författare)
  • Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis
  • 2007
  • Ingår i: Nat Med. - 1078-8956 (Print).
  • Tidskriftsartikel (refereegranskat)abstract
    • Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy.
  • Zepeda-Romero, L. C., et al. (författare)
  • Oxygen Monitoring Reduces the Risk for Retinopathy of Prematurity in a Mexican Population
  • 2016
  • Ingår i: Neonatology. - 1661-7800. ; 110:2, s. 135-140
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High levels of oxygen saturation are a well-known risk factor for ROP. Objectives: To assess the frequency of ROP type 1 needing treatment after improved oxygen monitoring (2011) in a Mexican preterm population selected for WINROP analyses and to retrospectively revalidate WINROP, an online surveillance system identifying infants at risk of developing ROP type 1. Methods: Preterm infants born with birth weight (BW) < 1,750 g and/or at gestational age (GA) <= 34 weeks, screened for ROP in 2012-2014 at the Hospital Civil de Guadalajara, Mexico were included (n = 151). Eighty-five infants with GA < 32 weeks qualified for WINROP analyses. GA, BW, maximal ROP stage, ROP treatment and weekly weights were recorded. The results in the present study were compared to those of a previous WINROP study in the same hospital (2005-2010; n = 352). Results: In the present WINROP cohort, 11.8% of the infants born at GA < 32 weeks received treatment compared to 51.0% of the infants in the previous WINROP cohort. One infant (3%) born at GA >= 32 weeks received treatment during the present study period compared to 35.6% during the previous period. WINROP displayed 80.0% sensitivity in infants born at GA < 32 weeks in the present study compared to 84.7% in the previous study. Conclusions: Uncontrolled oxygen supplementation is the major risk factor for severe ROP in infants born at GA >= 32 weeks. After improved oxygen monitoring, the frequency of ROP treatment was dramatically reduced at the Hospital Civil de Guadalajara, Mexico. (C) 2016 S. Karger AG, Basel.
  • Zepeda-Romero, L. C., et al. (författare)
  • Prediction of Retinopathy of Prematurity Using the Screening Algorithm WINROP in a Mexican Population of Preterm Infants
  • 2012
  • Ingår i: Archives of Ophthalmology. - 0003-9950. ; 130:6, s. 720-723
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To retrospectively validate the WINROP (weight, insulin-like growth factor I, neonatal, retinopathy of prematurity [ROP]) algorithm in identification of type 1 ROP in a Mexican population of preterm infants. Methods: In infants admitted to the neonatal intensive care unit at Hospital Civil de Guadalajara from 2005 to 2010, weight measurements had been recorded once weekly for 192 very preterm infants (gestational age [GA] <32 weeks) and for 160 moderately preterm infants (GA >= 32 weeks). Repeated eye examinations had been performed and maximal ROP stage had been recorded. Data are part of a case-control database for severe ROP risk factors. Results: Type 1 ROP was found in 51.0% of very preterm and 35.6% of moderately preterm infants. The WINROP algorithm correctly identified type 1 ROP in 84.7% of very preterm infants but in only 5.3% of moderately preterm infants. For infants with GA less than 32 weeks, the specificity was 26.6%, and for those with GA 32 weeks or more, it was 88.3%. Conclusions: In this Mexican population of preterm infants, WINROP detected type 1 ROP early in 84.7% of very preterm infants and correctly identified 26.6% of infants who did not develop type 1 ROP. Uncertainties in dating of pregnancies and differences in postnatal conditions may be factors explaining the different outcomes of WINROP in this population.
  • Fu, Z. J., et al. (författare)
  • Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid Protection Against Choroidal Neovascularization in Mice
  • 2017
  • Ingår i: Investigative Ophthalmology & Visual Science. - 0146-0404. ; 58:10, s. 3862-3870
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Neovascular age-related macular degeneration (AMD) is a major cause of legal blindness in the elderly. Diets with omega3-long-chain-polyunsaturated-fatty-acid (omega 3-LCPUFA) correlate with a decreased risk of AMD. Dietary omega 3-LCPUFA versus omega 6-LCPUFA inhibits mouse ocular neovascularization, but the underlying mechanism needs further exploration. The aim of this study was to investigate if adiponectin (APN) mediated x omega 3-LCPUFA suppression of neovessels in AMD. METHODS. The mouse laser-induced choroidal neovascularization (CNV) model was used to mimic some of the inflammatory aspect of AMD. CNV was compared between wild-type (WT) and Apn(-/-) mice fed either otherwise matched diets with 2% x3 or 2% omega 6-LCPUFAs. Vldlr(-/-) mice were used to mimic some of the metabolic aspects of AMD. Choroid assay ex vivo and human retinal microvascular endothelial cell (HRMEC) proliferation assay in vitro was used to investigate the APN pathway in angiogenesis. Western blot for p-AMPK alpha/AMPK alpha and qPCR for Apn, Mmps, and IL-10 were used to define mechanism. RESULTS. omega 3-LCPUFA intake suppressed laser-induced CNV in WT mice; suppression was abolished with APN deficiency. omega 3-LCPUFA, mediated by APN, decreased mouse Mmps expression. APN deficiency decreased AMPK alpha phosphorylation in vivo and exacerbated choroid-sprouting ex vivo. APN pathway activation inhibited HRMEC proliferation and decreased Mmps. In Vldlr(-/-) mice, omega 3-LCPUFA increased retinal AdipoR1 and inhibited NV. omega 3-LCPUFA decreased IL-10 but did not affect Mmps in Vldlr(-/-) retinas. CONCLUSIONS. APN in part mediated omega 3-LCPUFA inhibition of neovascularization in two mouse models of AMD. Modulating the APN pathway in conjunction with a omega 3-LCPUFA-enriched-diet may augment the beneficial effects of omega 3-LCPUFA in AMD patients.
  • Löfqvist, Chatarina, 1964-, et al. (författare)
  • IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth
  • 2007
  • Ingår i: Proc Natl Acad Sci U S A. - 0027-8424 (Print). ; 104:25, s. 10589-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Vessel loss precipitates many diseases. In particular, vessel loss resulting in hypoxia induces retinal neovascularization in diabetic retinopathy and in retinopathy of prematurity (ROP), major causes of blindness. Here we define insulin-like growth factor binding protein-3 (IGFBP3) as a new modulator of vascular survival and regrowth in oxygen-induced retinopathy. In IGFBP3-deficient mice, there was a dose-dependent increase in oxygen-induced retinal vessel loss. Subsequent to oxygen-induced retinal vessel loss, Igfbp3(-/-) mice had a 31% decrease in retinal vessel regrowth versus controls after returning to room air. No difference in serum insulin-like growth factor 1 (IGF1) levels was observed among groups. Wild-type mice treated with exogenous IGFBP3 had a significant increase in vessel regrowth. This correlated with a 30% increase in endothelial progenitor cells in the retina at postnatal day 15, indicating that IGFBP3 could be serving as a progenitor cell chemoattractant. In a prospective clinical study, we measured IGFBP3 (and IGF1) plasma levels weekly and examined retinas in all premature infants born at gestational ages <32 weeks at high risk for ROP. The mean level of IGFBP3 at 30-35 weeks postmenstrual age (PMA) for infants with proliferative ROP (ROP stages 3>, n = 13) was 802 microg/liter, and for infants with no ROP (ROP stage 0, n = 38) the mean level was 974 microg/liter (P < 0.03). These results suggest that IGFBP3, acting independently of IGF1, helps to prevent oxygen-induced vessel loss and to promote vascular regrowth after vascular destruction in vivo in a dose-dependent manner, resulting in less retinal neovascularization.
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