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Zhongjie Fu, Chatarina Lofqvist, Christian G Hurst, Zhenghao Cui, Lucy P Evans, Katherine T Tian, Hannah H Bogardus, Jing Chen, Ann Hellström, Lois Smith; Adiponectin mediates protective effect of omega-3 long-chain polyunsaturated fatty acid in retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3558.
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Retinopathy of prematurity (ROP) is a common blinding disease in premature infants. It is caused by inadequate retinal vascularization, resulting in retinal ischemia stimulating vision-threatening vaso-proliferative ROP. Lack of factors normally available in the third trimester of pregnancy in utero, and lacking after preterm birth such as omega-3 long-chain polyunsaturated fatty acid (ω-3 LCPUFA), is associated with development of retinopathy. Dietary supplement of ω-3 LCPUFA is protective in a mouse model of ROP. Our preliminary data show that adiponectin (APN), an adipocytokine abundantly expressed in white adipose tissue (WAT), is significantly lower in serum from preterm infants with ROP versus without ROP. We aimed to determine whether decreased APN levels in ROP are associated with deficiency of ω-3 LCPUFA, and if APN mediates in part the protective effect of ω-3 LCPUFA in ROP.
In the mouse model of oxygen-induced retinopathy (OIR), APN-knockout (APN-/-) and wild-type (WT) mice were fed isocaloric diets enriched with either ω-3 or ω-6 from postnatal day (P)1. Pups were sacrificed at P17 for serum and WAT APN levels, retinal vaso-obliteration and neovascularization. APN and its receptors were examined with immunohistochemistry, endoplasmic reticulum (ER) stress markers and ER proteins were examined in WAT using Western Blot.
In OIR, dietary ω-3 LCPUFA feed increased serum (ω-3: 5.8±1.4μg/ml vs. ω-6: 1.3±0.6μg/ml, P<0.05) and WAT APN level (ω-3: 0.30±0.02ng/μg vs. ω-6: 0.23±0.02ng/μg, P<0.05) at P17 compared with ω-6 feed. Moreover, the vaso-protective effect of ω-3 LCPUFA in OIR observed in WT retinae (neovascular area ω-3/ω-6=0.3, P<0.001) versus ω-6 feed was abolished in APN-/- retinae (neovascular area ω-3/ω-6=0.9, P<0.05). APN and its receptors were localized in endothelial cells and macrophages in both neovascular areas in OIR. ER stress (p-eIF2α/eIF2α: ω-3/ω-6=0.4, P<0.05; CHOP: ω-3/ω-6=0.5, P<0.01) was attenuated and ER protein was increased (Erp44: ω-3/ω-6=1.9, P<0.05) in WAT from ω-3 LCPUFA-fed mice versus ω-6 LCPUFA-fed mice
An increase in dietary ω-3 LCPUFA may regulate production of APN through modulating ER stress in WAT and APN in turn likely mediates in part the protective effects of ω-3 LCPUFA in OIR
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