Evidence map›Paper›PMID 40049514›Full record

ArticleJournal of advanced research2025

Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation.

Myriam Boeck, Hitomi Yagi, Chuck T Chen, Yan Zeng, Deokho Lee, Shen Nian, Taku Kasai, Jeff Lee, Victoria Hirst, Chaomei Wang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Myriam BoeckDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, 79106 Germany.
Hitomi YagiDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Keio University School of Medicine, 160-8582 Tokyo, Japan.
Chuck T ChenDepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto M5S 1A8 ON, Canada.
Yan ZengDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Deokho LeeDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Shen NianDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Xi'an Medical University, Xi'an, Shaanxi Province, 710021, China.
Taku KasaiCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jeff LeeDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Victoria HirstDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Chaomei WangDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Katherine NeilsenDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Tori C RodrickMetabolomics Core Resource Laboratory, NYU Langone Health, New York, NY 10016, USA.
Andrew McCutcheonDepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto M5S 1A8 ON, Canada.
Mathew YuDepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto M5S 1A8 ON, Canada.
Irfan J LodhiDivision of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University, St. Louis, MO 63110, USA.
Sasha A SinghCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Masanori AikawaCenter 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, USA.
Richard P BazinetDepartment of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto M5S 1A8 ON, Canada.
Zhongjie FuDepartment of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: zhongjie.fu@childrens.harvard.edu.

Funding

Dietary control of angiogenesis in retinopathy modelsR01EY017017 · NEI · BOSTON CHILDREN'S HOSPITAL · PI Zhongjie Fu, Lois Smith · 2006 to 2026
$11.8M
Serine control of retinal neovascularization in retinopathyR01EY032492 · NEI · BOSTON CHILDREN'S HOSPITAL · PI FU, ZHONGJIE · 2021 to 2025
$2.2M
BCFA Metabolism and the Regulation of Energy BalanceR01DK133344 · NIDDK · WASHINGTON UNIVERSITY · PI Irfan J Lodhi, Clay F. Semenkovich · 2023 to 2026
$2.0M
NEI NIH HHS R01 EY017017NEI NIH HHS R01 EY032492NIDDK NIH HHS R01 DK133344
6 · The paper itself

Abstract

introductionDyslipidemia contributes to many retinal diseases, but underlying lipid processing pathways are not fully understood. Peroxisomes oxidize very long-chain fatty acids and generate docosahexaenoic acid (DHA). Mutations in peroxisomal genes can result in severe neural retinal dysfunction. However, therapeutic approaches for peroxisomal diseases remain scarce, and dietary strategies yield inconsistent results.

objectivesThis study sought to elucidate retinal metabolic adaptations resulting from impaired peroxisomal fatty acid oxidation and to evaluate the therapeutic potential of nutrient supplementation in peroxisomal retinal disease.

methodsIn mice with global knockout (KO) of acyl-coenzyme A oxidase 1 (Acox1), encoding the first and rate-limiting enzyme in peroxisomal fatty acid oxidation, the retina was characterized at postnatal day (P) 30 during development. Retinal thickness, photoreceptor structure, and function were examined. Proteome analysis was utilized for molecular mechanistic investigation. Metabolomics and fatty acid profiling were conducted to study metabolic alterations in the retina. Nutrient intervention was performed to test if providing deficient nutrients could attenuate the observed retinal dysfunction.

resultsIn P30 Acox1 KO mice, we observed impaired neural retinal signaling, accompanied by reduced expression of genes involved in phototransduction. Proteomics suggested diminished glucose and mitochondrial metabolism, supported by decreased mitochondrial number and mitochondrial DNA copy number. Metabolomics showed reduced abundance of retinal pyruvate, and pyruvate supplementation from P30-P60 attenuated neural retinal dysfunction in Acox1 KO mice at P60. Furthermore, Acox1 KO mice at P30 exhibited a significant decrease in omega-3 (n-3) fatty acids and a compensatory increase in n-6 fatty acids. Dietary supplementation with DHA (n-3) or DHA plus arachidonic acid (n-6) from P30-P60 mitigated the progression of retinal dysfunction in Acox1 KO mice.

conclusionRetinal dysfunction, decreased mitochondrial number, and metabolic imbalance were observed in mice with impaired peroxisomal fatty acid oxidation. Nutrient intervention may offer a promising therapeutic approach for peroxisomal diseases.

Indexed as

Acyl-CoA OxidaseDietary SupplementsFatty AcidsPeroxisomesRetinaRetinal DiseasesAnimalsMiceMice, Inbred C57BLMice, KnockoutOxidation-ReductionACOX1 protein, mouseAcyl-CoA OxidaseFatty AcidsACOX1DHADyslipidemiaPeroxisomesRetinal degenerationRetinal metabolism

Identifiers

PMID40049514
PMCPMC12684955

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.