Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis
Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis
复制标题
DOI：
10.1038/nm1591
复制
发表时间：
2007-07-01
期刊：
影响因子：
82.9
通讯作者：
Smith, Lois E. H.
中科院分区：
文献类型：
--
作者：
Connor, Kip M.;SanGiovanni, John Paul;Smith, Lois E. H.
许多威胁视力的疾病有两个关键阶段，血管损失，其次是缺氧驱动的破坏性新血管形成。这些疾病包括早产儿视网膜病变和糖尿病视网膜病变，这是影响美国400多万人的儿童和中年失明的主要原因。我们研究了omega-3-和omega-6-多不饱和脂肪酸（PUFAs）对氧诱导视网膜病变小鼠模型中血管损失、损伤后血管再生和缺氧诱导的病理性新生血管形成的影响。我们发现，通过饮食或遗传手段增加omega-3-PUFA组织水平，通过增加损伤后血管再生减少了视网膜的无血管区域，从而减少了新生血管形成的缺氧刺激。生物活性的ω-3-PUFA衍生的介质neuroprotectinD 1、resolvinD 1和resolvinE 1也有效地防止新生血管形成。omega-3-PUFA及其生物活性代谢物的保护作用部分通过抑制肿瘤坏死因子-α介导。这种炎性细胞因子存在于与视网膜血管密切相关的小胶质细胞亚群中。这些发现表明，增加omega-3-PUFA或其生物活性产物的来源可减少病理性血管生成。西方饮食通常缺乏omega-3-PUFA，早产儿缺乏通常发生在妊娠晚期的omega-3-PUFA从母亲到婴儿的重要转移。补充omega-3-PUFA摄入量可能有助于预防视网膜病变。
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.