Dietary control of angiogenesis in retinopathy models

视网膜病变模型中血管生成的饮食控制

基本信息

批准号：
10683356
负责人：
Zhongjie Fu
金额：
$ 51.92万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10683356
关键词：
Address Affect Arachidonic Acids Area Attenuated Blood Blood Vessels Carbon Cells Circulation Clinical Data Development Diet Disease Docosahexaenoic Acids Docosahexaenoic acid supplement Docosahexaenoic acid supplementation Energy Metabolism Fatty Acids Fibroblast Growth Factor Glucose Glycolysis Grant Growth Growth Factor Hyperglycemia Hyperglycemic Mice Infant Intervention Knowledge Lipids Metabolic Metabolism Mitochondria Modeling Morphology Mus Mutant Strains Mice Neuronal Dysfunction Neurons Neurophysiology - biologic function Oral Oxygen Pathway interactions Phase Photoreceptors Physiological Physiology Pilot Projects Platelet-Derived Growth Factor Polyunsaturated Fatty Acids Premature Birth Premature Infant Reporting Respiration Retina Retinal Diseases Retinopathy of Prematurity Risk Factors Role Serum Signal Transduction Structure Testing Vascular Endothelial Growth Factors Vascularization Work adiponectin angiogenesis cell type dietary dietary control extreme prematurity fatty acid oxidation improved in utero lipidomics metabolomics mitochondrial metabolism neovascular neovascularization neuronal metabolism neurovascular novel oral supplementation oxidation postnatal preservation prevent response retina blood vessel structure retinal neuron transcriptome sequencing transcriptomics

项目摘要

Retinopathy of prematurity (ROP) affects ~16,000 premature infants per year in the US. At preterm birth, there is loss of both ω3 and ω6 long-chain polyunsaturated fatty acid (LCPUFA), normally provided by the maternal/placental interface in utero. prominently contributes to initiation and progression of ROP. Docosahexaenoic acid (DHA, ω3) alone prevents ROP in some but not all studies. If DHA is given alone serum arachidonic acid (AA, ω6) decreases further, and lack of AA also contributes to ROP. We must understand how DHA and AA together prevent ROP to develop potent safe interventions based on physiology. In premature infants developing severe ROP, decreased mitochondrial number and increased peroxisomal activity (cleaving lipids ≥22 carbons) was found. However, knowledge of mitochondrial and peroxisomal lipid oxidation in retinal diseases is limited. Pilot work suggests DHA and AA control peroxisomal activity in a phase 1 ROP model. We will determine DHA/AA effects on retinal metabolism, particularly mitochondrial and peroxisomal fatty acid oxidation in early vessel loss in ROP. DHA/AA controls neurovascular development in phase 1 ROP by improving metabolism. In hyperglycemic mice in phase I ROP (vessel growth suppression and retinal neuronal dysfunction) we will: i) investigate if AA adds to DHA protection against retinal neurovascular abnormalities; ii) determine if DHA/AA alters retinal mitochondrial metabolism, and iii) determine if DHA/AA controls peroxisomal β-fatty acid oxidation. SUMMARY: These studies will determine if AA adds to DHA protection in phase I ROP (improving retinal metabolism) and uncover novel lipid metabolic associations. Supplementing DHA and AA orally will likely help prevent ROP and other retinopathies

在美国，早产儿视网膜病变 (ROP) 每年影响约 16,000 名早产儿。早产，ω3和ω6长链多不饱和脂肪酸（LCPUFA）都会损失，通常由子宫内的母体/胎盘界面提供。单独的二十二碳六烯酸 (DHA, ω3) 可以预防 ROP 的发生和进展。一些但不是全部研究表明，如果单独给予 DHA，血清花生四烯酸 (AA, ω6) 会降低。此外，缺乏 AA 也会导致 ROP。我们必须了解 DHA 和 AA 是如何结合在一起的。预防早产儿 ROP，根据生理学制定有效的安全干预措施。发生严重的 ROP、线粒体数量减少和过氧化物酶体活性增加（裂解脂质≥22个碳）然而，线粒体和过氧化物酶体的知识。视网膜疾病中的脂质氧化是有限的，试点工作表明 DHA 和 AA 的控制。我们将确定 DHA/AA 对视网膜的影响。代谢，特别是早期血管损失中的线粒体和过氧化物酶体脂肪酸氧化在 ROP 中。 DHA/AA 通过改善 ROP 1 期神经血管发育来控制神经血管发育代谢。在高血糖小鼠中，处于 I 期 ROP（血管生长抑制和视网膜神经元功能障碍）我们将： i）研究 AA 是否会增加 DHA 对视网膜神经血管的保护作用异常；ii) 确定 DHA/AA 是否改变视网膜线粒体代谢，以及 iii) 确定 DHA/AA 是否控制过氧化物酶体 β-脂肪酸氧化。摘要：这些研究将确定 AA 是否会在 I 期 ROP 中增加 DHA 保护（改善视网膜代谢）并发现新的脂质代谢关联。口服 DHA 和 AA 可能有助于预防 ROP 和其他视网膜病变

项目成果

期刊论文数量（55）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The biology of retinopathy of prematurity: how knowledge of pathogenesis guides treatment.

DOI：
10.1016/j.clp.2013.02.002
发表时间：
2013-06
期刊：
Clinics in perinatology
影响因子：
2.1
作者：
Smith LE;Hard AL;Hellström A
通讯作者：
Hellström A

Retinopathy of prematurity: current concepts in molecular pathogenesis.

DOI：
10.1080/08820530902800314
发表时间：
2009-03
期刊：
Seminars in ophthalmology
影响因子：
1.7
作者：
Heidary G;Vanderveen D;Smith LE
通讯作者：
Smith LE

Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy.

DOI：
10.1161/circresaha.110.221317
发表时间：
2010-08-20
期刊：
Circulation research
影响因子：
20.1
作者：
Stahl A;Sapieha P;Connor KM;Sangiovanni JP;Chen J;Aderman CM;Willett KL;Krah NM;Dennison RJ;Seaward MR;Guerin KI;Hua J;Smith LE
通讯作者：
Smith LE

Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?

DOI：
10.1007/s12975-017-0539-1
发表时间：
2017-06-10
期刊：
Translational stroke research
影响因子：
6.9
作者：
Agyemang AA;Sveinsdóttir K;Vallius S;Sveinsdóttir S;Bruschettini M;Romantsik O;Hellström A;Smith LEH;Ohlsson L;Holmqvist B;Gram M;Ley D
通讯作者：
Ley D

Retinopathy of prematurity: the need for prevention.