Dietary control of angiogenesis in retinopathy models

在美国，每年约有16,000名早产儿患上早产儿视网膜病变(ROP)。在… 早产，ω3长链多不饱和脂肪酸的丢失，通常由 母体/胎盘界面在ROP的发生和发展中起着重要作用。 ω3LCPUFA和葡萄糖代谢之间的联系还没有被探索，尽管在 人ROP，I期高血糖(血管丢失或血管发育受阻) 与视网膜病变的进展密切相关。在小鼠身上，我们发现 高血糖延迟视网膜血管发育(I期ROP)，这对 用膳食ω3LCPUFAs减重。定义ω3LCPUFA和葡萄糖之间的联系 我们把目光投向了一种重要的脂肪细胞衍生激素和代谢调节剂， 脂联素(APN)。早产儿低ω-3LCPUFA、低血清脂蛋白和高血糖 均与ROP的发生发展有关。我们将探讨ω3LCPUFA对 ROP早期血管丢失的高血糖加重及激素在其中的作用 ω3LCPUFA对高血糖视网膜病变的保护作用。 ω3LCPUFA通过调节脂/糖代谢预防高血糖诱导的ROP APN 在处于I期ROP(血管生长抑制)的高血糖小鼠中，我们将：i)ω3LCPUFA 预防高血糖导致的视网膜发育抑制(I期ROP)；II) ω3LCPUFA保存测定视网膜及血管糖脂代谢调节 高血糖时的血管，以及iii)确定APN是否介导ω3LCPUFA血管和 新生儿高血糖时视网膜神经元的保护作用。 摘要：这些研究将确定ω3LCPUFA的代谢控制(通过脂质 相关激素)导致高血糖，从而增加ROP风险。荷尔蒙调节是 可能导致ROP的新的预防方法和治疗选择，并具有治疗性 对许多其他疾病的影响。

Retinopathy of prematurity (ROP) affects ~16,000 premature infants per year in the US. At preterm birth, loss of ω3 long-chain polyunsaturated fatty acid (LCPUFA), normally provided by the maternal/placental interface prominently contributes to initiation and progression of ROP. The link between ω3LCPUFA and glucose metabolism has not been explored although in human ROP, hyperglycemia during phase I (vessel loss or suppression of vessel development) is very strongly associated with retinopathy progression. In mouse pups we found that hyperglycemia delayed retinal vascular development (phase I ROP) which was greatly attenuated with dietary ω3LCPUFAs. To define the link between ω3LCPUFA and glucose control we looked to an important adipocyte-derived hormone and metabolic regulator, adiponectin (APN). In premature infants, low ω-3LCPUFA, low serum APN, and hyperglycemia are all correlated with development of ROP. We will explore ω3LCPUFA effects on hyperglycemic exacerbation of early vessel loss in ROP and the role of hormones in ω3LCPUFA protection against hyperglycemic retinopathy. ω3LCPUFA regulates lipid/glucose metabolism to prevent hyperglycemia-induced ROP through APN In hyperglycemic mice in phase I ROP (vessel growth suppression) we will: i) ω3LCPUFA protects against hyperglycemia-induced suppression of retinal development (phase I ROP); ii) determine retinal and vessel glucose/lipid metabolic regulation with ω3LCPUFA preservation of vessels during hyperglycemia, and iii) determine if APN mediates ω3LCPUFA vascular and neuronal retina protection in neonatal hyperglycemia. SUMMARY: These studies will determine ω3LCPUFA metabolic control (through lipid associated hormones) of hyperglycemia, which increases ROP risk. Hormonal modulation is likely to lead to new preventive approaches and treatment options for ROP and has therapeutic implications for many other diseases.