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。 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作用有限。试点工作表明 DHA 和 AA 的控制是有限的。 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

Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy.

出生后体重增加会改变氧诱导的增殖性视网膜病变的严重程度和功能结果。

• DOI: 10.2353/ajpath.2010.100526
• 发表时间: 2010-12-01
• 期刊: The American journal of pathology
• 作者: A. Stahl;Jing Chen;P. Sapieha;Molly R. Seaward;N. Krah;R. J. Dennison;Tara L. Favazza;Felicitas Bucher;Chatarina Löfqvist;H. Ong;A. Hellström;S. Chemtob;James D. Akula;Lois E. H. Smith
• 通讯作者: Lois E. H. Smith

Retinopathy of prematurity: current concepts in molecular pathogenesis.

早产儿视网膜病变：分子发病机制的当前概念。

• 发表时间: 2009-03
• 作者: Heidary, Gena;Vanderveen, Deborah;Smith, Lois E
• 通讯作者: Smith, Lois E

Ghrelin modulates physiologic and pathologic retinal angiogenesis through GHSR-1a.

Ghrelin 通过 GHSR-1a 调节生理和病理性视网膜血管生成。

• 发表时间: 2011-07
• 影响因子: 4.4
• 作者: Zaniolo, Karine;Sapieha, Przemyslaw;Shao, Zhuo;Stahl, Andreas;Zhu, Tang;Tremblay, Sophie;Picard, Emilie;Madaan, Ankush;Blais, Martine;Lachapelle, Pierre;Mancini, Joseph;Hardy, Pierre;Smith, Lois E H;Ong, Huy;Chemtob, Sylvain
• 通讯作者: Chemtob, Sylvain

Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity.

出生后早期体重增加对极早产儿正常视网膜血管生成的重要性：一项多中心研究分析体重速度偏差以预测早产儿视网膜病变。

• 发表时间: 2012-08
• 作者: Wu, Carolyn;Löfqvist, Chatarina;Smith, Lois E H;VanderVeen, Deborah K;Hellström, Ann;WINROP Consortium
• 通讯作者: WINROP Consortium

DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ω-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways.

PPARGC1A（一种编码α-3 LCPUFA 感应 PPAR-RXR 转录复合物的共激活子的基因）中的 DNA 序列变异与补体和 VEGF 信号通路基因中的 NV AMD 和 AMD 相关位点相关。

• 发表时间: 2013
• 影响因子: 3.7
• 作者: SanGiovanni, John Paul;Chen, Jing;Sapieha, Przemyslaw;Aderman, Christopher M;Stahl, Andreas;Clemons, Traci E;Chew, Emily Y;Smith, Lois E H
• 通讯作者: Smith, Lois E H