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，预期病（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）丧失， 通常由子宫中的母亲/胎盘界面提供。突出贡献 ROP的启动和进展。仅二十六烯酸（DHA，ω3）就可以防止ROP进入 一些但不是全部研究。如果单独给出DHA，血清蛛网膜酸（AA，ω6）下降 此外，缺乏AA也有助于ROP。我们必须了解DHA和AA如何在一起 防止ROP基于生理学开发潜在的安全干预措施。在早产婴儿中 发展严重的ROP，线粒体数量降低和过氧化物体活性增加 （切割脂质≥22碳）。但是，有线粒体和过氧化物体的知识 残留疾病中的脂质氧化有限。飞行员工作建议DHA和AA控制 1期ROP模型中的过氧活性。我们将确定DHA/AA对残差的影响 早期血管损失中的线粒体和过氧化物体脂肪酸氧化的代谢，特别是线粒体和过氧化物体脂肪酸 在ROP中。 DHA/AA通过改善1阶段ROP中的神经血管发育 代谢。 在I期ROP中的高血糖小鼠中（血管生长抑制和永久神经元 功能障碍）我们将：i）调查AA是否增加了DHA防止残留神经血管的保护 异常； ii）确定DHA/AA是否改变了视网膜线粒体代谢，iii） 确定DHA/AA是否控制过氧化物体β-脂肪酸氧化。 摘要：这些研究将确定AA是否在I期ROP中增加了DHA保护 （改善视网膜代谢）和发现新型的脂质代谢关联。补充 DHA和AA口服可能有助于防止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

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

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