Dietary control of angiogenesis in retinopathy models

视网膜病变模型中血管生成的饮食控制

• 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
• 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

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。在 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。显着贡献于 ROP 的启动和进展。二十二碳六烯酸 (DHA, ω3) 单独可预防 ROP 一些但不是全部研究。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如何结合在一起 预防 ROP，根据生理学制定有效的安全干预措施。对于早产儿 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）被发现。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。试点工作建议控制 DHA 和 AA 1 期 ROP 模型中的过氧化物酶体活性。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。补充 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

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

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

Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy.

• DOI: 10.1371/journal.pone.0085031
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Michan S;Juan AM;Hurst CG;Cui Z;Evans LP;Hatton CJ;Pei DT;Ju M;Sinclair DA;Smith LE;Chen J
• 通讯作者: Chen J

Retinopathy of prematurity: the need for prevention.

• DOI: 10.2147/eb.s99038
• 发表时间: 2016
• 期刊: Eye and brain
• 影响因子: 4.4
• 作者: Liegl R;Hellström A;Smith LE
• 通讯作者: Smith LE