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

Zhongjie Fu; Wenjun Yan; Chuck T. Chen; Anders K. Nilsson; Edward Bull; William Allen; Jay Yang; Minji Ko; John Paul SanGiovanni; James D. Akula; Saswata Talukdar; Ann Hellström; Lois E. H. Smith

doi:10.3390/nu14071333

Nutrients (Mar 2022)

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

Zhongjie Fu,
Wenjun Yan,
Chuck T. Chen,
Anders K. Nilsson,
Edward Bull,
William Allen,
Jay Yang,
Minji Ko,
John Paul SanGiovanni,
James D. Akula,
Saswata Talukdar,
Ann Hellström,
Lois E. H. Smith

Affiliations

Zhongjie Fu: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Wenjun Yan: Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Chuck T. Chen: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20814, USA
Anders K. Nilsson: Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden
Edward Bull: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
William Allen: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Jay Yang: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Minji Ko: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
John Paul SanGiovanni: BIO5 Institute, Department of Nutritional Sciences, The University of Arizona, Tucson, AZ 85721, USA
James D. Akula: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Saswata Talukdar: Cardiometabolic Diseases, Merck Research Laboratories, Boston, MA 02115, USA
Ann Hellström: Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 412 96 Gothenburg, Sweden
Lois E. H. Smith: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA

DOI: https://doi.org/10.3390/nu14071333
Journal volume & issue: Vol. 14, no. 7
p. 1333

Abstract

Read online

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.

Published in Nutrients

ISSN: 2072-6643 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Technology: Home economics: Nutrition. Foods and food supply
Website: https://www.mdpi.com/journal/nutrients

About the journal

Abstract

Keywords