Lack of dietary DHA drives harmful lipid remodeling and retinal degeneration in mice
Restoring the fatty acid reversed visual decline in mice and cleared toxic oxidized lipids that otherwise trigger chronic microglial activation.
bioRxiv · Hagimori R et al. · Paper published 28 Sep 2026
In a preprint study, researchers found that chronic DHA deficiency in mice triggers a neural-tissue-selective lipid shift from DHA-containing phospholipids to oxidation-prone omega-6 species. This remodeling increased lipid peroxidation and oxidative damage in the retina, driving inflammation and visual dysfunction. Dietary DHA restoration successfully reversed these pathological shifts, oxidative stress, and visual problems in the animals. The team also uncovered an APOE-dependent clearance pathway that shunts oxidized lipids from the neural retina to subretinal microglia. Chronic lipid uptake overwhelmed microglial lysosomes, causing persistent galectin-3 activation that promoted tissue breakdown. Deleting galectin-3 protected against this late-stage degeneration, and physiologically aged mouse retinas exhibited the same shift toward omega-6 lipid accumulation.
Why it matters
The findings define a specific pathway linking declining DHA availability to lipid peroxidation, microglial dysfunction, and age-related neural decline.
Caveats
The study was conducted in mice, and its findings have been published as a preprint that has not yet undergone peer review.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
DHA deficiency drives neural oxidized-lipid stress and microglial activation
Hagimori R, Gogoi P, Shahi PK et al.
bioRxiv · 28 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
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- Preprint
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