Combined 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...
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Elsevier
2025-09-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825003020 |
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| author | Myriam Boeck Hitomi Yagi Pia Lundgren Aldina Pivodic Anders K. Nilsson Yan Zeng Chuck T. Chen Taku Kasai Deokho Lee Shen Nian Victoria Hirst Katherine Neilsen Chaomei Wang Jeff Lee Mathew Yu Andrew McCutcheon Sasha A. Singh Masanori Aikawa Richard P. Bazinet Zhongjie Fu Ann Hellström Lois EH Smith |
| author_facet | Myriam Boeck Hitomi Yagi Pia Lundgren Aldina Pivodic Anders K. Nilsson Yan Zeng Chuck T. Chen Taku Kasai Deokho Lee Shen Nian Victoria Hirst Katherine Neilsen Chaomei Wang Jeff Lee Mathew Yu Andrew McCutcheon Sasha A. Singh Masanori Aikawa Richard P. Bazinet Zhongjie Fu Ann Hellström Lois EH Smith |
| author_sort | Myriam Boeck |
| collection | DOAJ |
| description | 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 ROP). At postnatal day (P) 10, retinal vessel growth was improved in pups from mothers on diets enriched with 1 % DHA + 2 % ARA vs. 3 % DHA. Lipid changes in pup plasma and RPE complex (retinal pigment epithelium with choroid and sclera) were in accordance with maternal diets' DHA and ARA levels, indicating that milk lipids reflected maternal diets. Proteomic retinal analysis revealed increased abundances of proteins related to mitochondrial respiration and glucose metabolism with the combined diet. Inhibition of mitochondrial ATP synthase negated the protective effects of the combined diet. In conclusion, combined DHA+ARA oral maternal supplementation protects against hyperglycemia-induced retinopathy in mouse neonates (Phase I ROP model) through enhanced retinal metabolism, suggesting the potential of balanced lipid supplementation for ROP prevention. |
| format | Article |
| id | doaj-art-5f031c8acb7d4c7595799ba861112a4d |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
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| series | Pharmacological Research |
| spelling | doaj-art-5f031c8acb7d4c7595799ba861112a4d2025-08-20T03:58:40ZengElsevierPharmacological Research1096-11862025-09-0121910787710.1016/j.phrs.2025.107877Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal miceMyriam Boeck0Hitomi Yagi1Pia Lundgren2Aldina Pivodic3Anders K. Nilsson4Yan Zeng5Chuck T. Chen6Taku Kasai7Deokho Lee8Shen Nian9Victoria Hirst10Katherine Neilsen11Chaomei Wang12Jeff Lee13Mathew Yu14Andrew McCutcheon15Sasha A. Singh16Masanori Aikawa17Richard P. Bazinet18Zhongjie Fu19Ann Hellström20Lois EH Smith21Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, JapanThe Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg 416 85, SwedenThe Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg 416 85, SwedenThe Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg 416 85, SwedenDepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USACenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USAThe Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg 416 85, SwedenDepartment of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Correspondence to: Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, 3 Blackfan Circle, CLS 18, Boston, MA 02115, USA.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 ROP). At postnatal day (P) 10, retinal vessel growth was improved in pups from mothers on diets enriched with 1 % DHA + 2 % ARA vs. 3 % DHA. Lipid changes in pup plasma and RPE complex (retinal pigment epithelium with choroid and sclera) were in accordance with maternal diets' DHA and ARA levels, indicating that milk lipids reflected maternal diets. Proteomic retinal analysis revealed increased abundances of proteins related to mitochondrial respiration and glucose metabolism with the combined diet. Inhibition of mitochondrial ATP synthase negated the protective effects of the combined diet. In conclusion, combined DHA+ARA oral maternal supplementation protects against hyperglycemia-induced retinopathy in mouse neonates (Phase I ROP model) through enhanced retinal metabolism, suggesting the potential of balanced lipid supplementation for ROP prevention.http://www.sciencedirect.com/science/article/pii/S1043661825003020Postnatal hyperglycemiaRetinopathy of prematurityDHAARARetinal vasculature |
| spellingShingle | Myriam Boeck Hitomi Yagi Pia Lundgren Aldina Pivodic Anders K. Nilsson Yan Zeng Chuck T. Chen Taku Kasai Deokho Lee Shen Nian Victoria Hirst Katherine Neilsen Chaomei Wang Jeff Lee Mathew Yu Andrew McCutcheon Sasha A. Singh Masanori Aikawa Richard P. Bazinet Zhongjie Fu Ann Hellström Lois EH Smith Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice Pharmacological Research Postnatal hyperglycemia Retinopathy of prematurity DHA ARA Retinal vasculature |
| title | Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice |
| title_full | Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice |
| title_fullStr | Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice |
| title_full_unstemmed | Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice |
| title_short | Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice |
| title_sort | combined dietary omega 3 and omega 6 fatty acids protect against hyperglycemia associated retinopathy in neonatal mice |
| topic | Postnatal hyperglycemia Retinopathy of prematurity DHA ARA Retinal vasculature |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825003020 |
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