Retinopathy of prematurity (ROP) affects ~16,000 premature infants per year in the US. At preterm birth, loss of ?3 long-chain polyunsaturated fatty acid (LCPUFA), normally provided by the maternal/placental interface prominently contributes to initiation and progression of ROP. The link between ?3LCPUFA 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 ?3LCPUFAs. To define the link between ?3LCPUFA and glucose control we looked to an important adipocyte-derived hormone and metabolic regulator, adiponectin (APN). In premature infants, low ?-3LCPUFA, low serum APN, and hyperglycemia are all correlated with development of ROP. We will explore ?3LCPUFA effects on hyperglycemic exacerbation of early vessel loss in ROP and the role of hormones in ?3LCPUFA protection against hyperglycemic retinopathy. ?3LCPUFA regulates lipid/glucose metabolism to prevent hyperglycemia-induced ROP through APN In hyperglycemic mice in phase I ROP (vessel growth suppression) we will: i) ?3LCPUFA protects against hyperglycemia-induced suppression of retinal development (phase I ROP); ii) determine retinal and vessel glucose/lipid metabolic regulation with ?3LCPUFA preservation of vessels during hyperglycemia, and iii) determine if APN mediates ?3LCPUFA vascular and neuronal retina protection in neonatal hyperglycemia. SUMMARY: These studies will determine ?3LCPUFA 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.
We will examine if ?3LCPUFA regulates lipid/glucose metabolism to prevent hyperglycemia- induced ROP through APN; little work has been done in this area. We have preliminarily found a profound beneficial effect of ?3LCPUFA on maintaining the retinal vascular formation during the hyperglycemia-induced early changes in phase I ROP and APN deficiency greatly abolished the protection. ?3LCPUFA supplement may prevent and treat hyperglycemic ROP.
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