Omega-3/Omega-6 Long-Chain Fatty Acid Imbalance in Phase I Retinopathy of Prematurity

• Published in: Nutrients 2022-03, Vol.14 (7), p.1333
• Main Authors: Fu, Zhongjie, Yan, Wenjun, Chen, Chuck T, Nilsson, Anders K, Bull, Edward, Allen, William, Yang, Jay, Ko, Minji, SanGiovanni, John Paul, Akula, James D, Talukdar, Saswata, Hellström, Ann, Smith, Lois E H
• Format: Article
• Language: English
• Subjects: activation steps; Adiponectin; Adiponectin - metabolism; Animals; arachidonic-acid; Birth weight; birth-weight infants; Blood vessels; Diet; docosahexaenoic acid; emulsion supplementation; Fatty acids; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Omega-3 - pharmacology; fish-oil; Gestational age; Glial cells; growth-factor-i; Humans; Hyperglycemia; Hyperglycemia - metabolism; Infant, Newborn; LCPUFA; lipid emulsions; Lipids; macular degeneration; Metabolism; Mice; Mimicry; Neonates; Neuronal-glial interactions; Newborn babies; Nutrition & Dietetics; Oftalmologi; Ophthalmology; Polyunsaturated fatty acids; Precipitates; Premature babies; Premature birth; Retina; Retina - metabolism; Retinal Neovascularization - metabolism; retinal neuron; retinal vessel; Retinopathy; Retinopathy of Prematurity; Transcriptomics; Vascularization; Vegetable oils
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14071333

There is a gap in understanding the effect of the essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy of prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to Phase I ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated Phase I retinopathy, dietary ω-3 (vs. ω-6 LCPUFA) supplementation promoted retinal vessel development. However, ω-6 (vs. ω-3 LCPUFA) was also developmentally essential, promoting neuronal growth and metabolism as suggested by a strong metabolic shift in almost all types of retinal neuronal and glial cells identified with single-cell transcriptomics. Loss of adiponectin (APN) in mice (mimicking the low APN levels in Phase I ROP) decreased LCPUFA levels (including ω-3 and ω-6) in retinas under normoglycemic and hyperglycemic conditions. ω-3 (vs. ω-6) LCPUFA activated the APN pathway by increasing the circulating APN levels and inducing expression of the retinal APN receptor. Our findings suggested that both ω-3 and ω-6 LCPUFA are crucial in protecting against retinal neurovascular dysfunction in a Phase I ROP model; adequate ω-6 LCPUFA levels must be maintained in addition to ω-3 supplementation to prevent retinopathy. Activation of the APN pathway may further enhance the ω-3 and ω-6 LCPUFA's protection against ROP.