Dietary control of angiogenesis in retinopathy models

早产儿视网膜病变（ROP）每年影响美国约16，000名早产儿。在 早产，ω 3长链多不饱和脂肪酸（LCPUFA）丢失，通常由 母体/胎盘界面对ROP的发生和发展有重要作用。 ω 3LCPUFA和葡萄糖代谢之间的联系尚未探讨，尽管在 人ROP，I期高血糖（血管损失或血管发育抑制） 与视网膜病变进展密切相关。我们发现， 高血糖延迟视网膜血管发育（I期ROP）， 用饮食ω 3LCPUFA减毒。确定ω 3LCPUFA和葡萄糖之间的联系 对照组，我们寻找一种重要的脂肪细胞来源的激素和代谢调节剂， 脂联素（APN）。在早产儿中，低ω-3 LCPUFA、低血清APN和高血糖 都与ROP的发生有关。我们将探讨ω 3LCPUFA对 视网膜病变早期血管丢失的高血糖加重及激素在其中的作用 ω 3LCPUFA对高血糖性视网膜病变的保护作用。 ω 3LCPUFA通过调节脂/糖代谢预防高血糖诱导的ROP APN 在I期ROP（血管生长抑制）的高血糖小鼠中，我们将：i）ω 3LCPUFA 防止高血糖诱导的视网膜发育抑制（I期ROP）; ii） 用ω 3LCPUFA保存测定视网膜和血管葡萄糖/脂质代谢调节， iii）确定APN是否介导ω 3LCPUFA血管和 新生儿高血糖时神经元视网膜保护作用 总结：这些研究将确定ω 3LCPUFA代谢控制（通过脂质 相关激素）的高血糖，这增加了ROP的风险。荷尔蒙调节是 可能导致ROP的新的预防方法和治疗选择， 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.