Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose–endoplasmic reticulum stress reduction to increase adiponectin

Abstract

Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

“…The biological impact of altering lipid intake is thought to be primarily through modification of membrane microdomain composition and specific receptors. Dietary ω3 to ω6 fatty acids may, therefore, impact retinal function and retinal neovascularization (Connor et al, 2007; Fu et al, 2015; Gong et al, 2015, 2016a, 2016b, 2017; Hård et al, 2013; Rezende et al, 2014; Sapieha et al, 2011, 2012; Shao et al, 2014; Stahl et al, 2010). There is no evidence these essential fatty acids are used for fuel, and without adequate synthetic machinery, it would be surprising if they were not used primarily in other capacities.…”

ER Stress and Angiogenesis

“…Diets rich in u-3 long-chain polyunsaturated fatty acids raise serum adiponectin levels, which inversely correlate with ROP severity (Fu et al, 2015). In OIR, ER stress within white adipose tissue leads to a drop in circulating bioactive high molecular weight adiponectin and hence poor prognosis.…”

“…In OIR, ER stress within white adipose tissue leads to a drop in circulating bioactive high molecular weight adiponectin and hence poor prognosis. Administration of dietary u-3 fatty acid was found to reverse activation of p-EIF2a or CHOP in adipocytes and consequently alleviate pathological retinal neovascularization in part through adiponectin synthesis and also through increased formation of bioactive high molecular weight forms (Fu et al, 2015). Therefore, systemic ER stress may remotely affect vascularization of peripheral tissues by impacting protein hormone synthesis and their assembly into bioactive forms.…”

Review: adiponectin in retinopathy

“…In lean, healthy individuals, APN is the most abundant adipokine in the plasma (3–30µg/ml), accounting for 0.01% of total plasma protein[16]. All three APN receptors: APN receptor 1 (AdipoR1), APN receptor 2 (AdipoR2), and T-cadherin are expressed in the mouse retina[3]. APN and AdipoR1, AdipoR2 are detected in the human retina[17].…”

“…Accumulating evidence shows that APN, which is another important metabolic modulator also derived mainly from adipocytes, is associated with many retinal metabolic disorders. Circulating APN levels are correlated with the development and progression of retinopathy of prematurity [3], diabetic retinopathy [4, 5], and age-related macular degeneration[6]. Animal studies indicate that increasing circulating APN levels suppress pathological vascular proliferation in rodent models of oxygen-induced proliferative retinopathy and laser-induced choroidal neovascularization[7, 8].…”