@article{7ac823d296234a65b7ee3391eda16981,
title = "Omega-3/Omega-6 Long-Chain Fatty Acid Imbalance in Phase I Retinopathy of Prematurity",
abstract = "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{\textquoteright}s protection against ROP.",
keywords = "Adiponectin, Hyperglycemia, LCPUFA, Retinal neuron, Retinal vessel, Retinopathy of prematurity",
author = "Zhongjie Fu and Wenjun Yan and Chen, {Chuck T.} and Nilsson, {Anders K.} and Edward Bull and William Allen and Jay Yang and Minji Ko and Sangiovanni, {John Paul} and Akula, {James D.} and Saswata Talukdar and Ann Hellstr{\"o}m and Smith, {Lois E.H.}",
note = "Funding Information: Acknowledgments: We thank the BPF Genomics Core Facility at Harvard Medical School for their expertise and instrument availability that supported this work. Work done by the Harvard Chan Bioinformatics Core was conducted in part with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. Funding Information: Funding: The research was funded by NIH R01EY017017, R01EY01717-13S1, R01EY030904, BCH IDDRC (1U54HD090255), Mass Lions Eye Foundation (LEHS); NIH R01EY032492, Boston Children{\textquoteright}s Hospital (OFD/BTREC/CTREC Faculty Career Development Grant 97906, Pilot Grant 92214, and Ophthalmology Foundation 85010), Mass Lions Eye Foundation 87820 (ZF); The Swedish Research Council (DNR# #2020-01092), government grants under the ALF agreement ALFGBG-717971, The Wallenberg Clinical Scholars (AH). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
month = apr,
day = "1",
doi = "10.3390/nu14071333",
language = "English (US)",
volume = "14",
journal = "Nutrients",
issn = "2072-6643",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",
}