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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Article number1333
Issue number7
StatePublished - Apr 1 2022


  • Adiponectin
  • Hyperglycemia
  • Retinal neuron
  • Retinal vessel
  • Retinopathy of prematurity

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics


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