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

Nutrients. 2022 Mar 23;14(7):1333. 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.

Keywords: LCPUFA; adiponectin; hyperglycemia; retinal neuron; retinal vessel; retinopathy of prematurity.

MeSH terms

  • Adiponectin / metabolism
  • Animals
  • Fatty Acids, Omega-3* / metabolism
  • Fatty Acids, Omega-3* / pharmacology
  • Humans
  • Hyperglycemia* / metabolism
  • Infant, Newborn
  • Mice
  • Retina / metabolism
  • Retinal Neovascularization* / metabolism
  • Retinopathy of Prematurity*


  • Adiponectin
  • Fatty Acids, Omega-3