biostudies-literatureBoeck MNEI NIH HHSNICHD NIH HHSNHLBI NIH HHS107877https://www.ebi.ac.uk/biostudies/studies/S-EPMC12445345biostudies-literatureUnknown219Retinopathy of prematurity (ROP) with early vessel loss (Phase I) followed by uncontrolled vessel growth (Phase II) causes visual impairment in premature infants. Although supplementation with omega-3 (n-3) docosahexaenoic acid (DHA) alone shows mixed results in preventing ROP, supplementation with both n-3 DHA and n-6 arachidonic acid (ARA) in early postnatal life reduces severe ROP by 50 % (Mega Donna Mega study). In the Mega Donna Mega study, 146 (72.6 %) of 201 included infants had at least one hyperglycemic episode during the first 14 days of life, which is a strong ROP risk factor. We therefore evaluated the protective effects and mechanisms of combined dietary n-3 DHA and n-6 ARA in a neonatal mouse model of hyperglycemia-induced suppression of retinal vascular development (Phase I Pharmacological researchCombined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice.PMC12445345R01 EY032492R01 EY017017R01 HL149302R01 HL126901U54 HD090255R01 EY030904Hirst VKasai TNeilsen KYu MWang CLee JFu ZAikawa MZeng YBoeck MLee DHellstrom ANilsson AKYagi HPivodic ANian SSingh SAChen CTBazinet RPLundgren PSmith LEMcCutcheon AfalseCombined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice.Retinopathy of prematurity (ROP) with early vessel loss (Phase I) followed by uncontrolled vessel growth (Phase II) causes visual impairment in premature infants. Although supplementation with omega-3 (n-3) docosahexaenoic acid (DHA) alone shows mixed results in preventing ROP, supplementation with both n-3 DHA and n-6 arachidonic acid (ARA) in early postnatal life reduces severe ROP by 50 % (Mega Donna Mega study). In the Mega Donna Mega study, 146 (72.6 %) of 201 included infants had at least one hyperglycemic episode during the first 14 days of life, which is a strong ROP risk factor. We therefore evaluated the protective effects and mechanisms of combined dietary n-3 DHA and n-6 ARA in a neonatal mouse model of hyperglycemia-induced suppression of retinal vascular development (Phase I 2025-01-01T00:00:00Z2025 Sep2026-06-03T16:52:11.596Z2026-04-29T03:13:15.115ZS-EPMC124453454070677710.1016/j.phrs.2025.107877