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J Biol Chem. 2017 Jul 21;292(29):12054-12064. doi: 10.1074/jbc.M117.790568. Epub 2017 Jun 3.

Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells.

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From the Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655,
the Departments of Lipid Science and.
the Agency for Medical Research and Development (AMED)-Core Research for Evolution Science and Technology (CREST), Chiyoda-ku, Tokyo 100-0004.
the Division of Molecular and Developmental Biology and.
the Department of Medical Biology, Akita University Graduate School of Medicine, Akita 010-8543.
the Research Center for Biosignal, Akita University Graduate School of Medicine, Akita 010-8502.
Akita Lipid Technologies, LLC, Akita 010-0825, and.
Medical Proteomics Laboratory, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639.
the Institute for Solid State Physics, University of Tokyo, Kashiwa, Chiba 277-8581, Japan.
From the Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655.
Lipidomics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033.


Docosahexaenoic acid (DHA) has essential roles in photoreceptor cells in the retina and is therefore crucial to healthy vision. Although the influence of dietary DHA on visual acuity is well known and the retina has an abundance of DHA-containing phospholipids (PL-DHA), the mechanisms associated with DHA's effects on visual function are unknown. We previously identified lysophosphatidic acid acyltransferase 3 (LPAAT3) as a PL-DHA biosynthetic enzyme. Here, using comprehensive phospholipid analyses and imaging mass spectroscopy, we found that LPAAT3 is expressed in the inner segment of photoreceptor cells and that PL-DHA disappears from the outer segment in the LPAAT3-knock-out mice. Dynamic light-scattering analysis of liposomes and molecular dynamics simulations revealed that the physical characteristics of DHA reduced membrane-bending rigidity. Following loss of PL-DHA, LPAAT3-knock-out mice exhibited abnormalities in the retinal layers, such as incomplete elongation of the outer segment and decreased thickness of the outer nuclear layers and impaired visual function, as well as disordered disc morphology in photoreceptor cells. Our results indicate that PL-DHA contributes to visual function by maintaining the disc shape in photoreceptor cells and that this is a function of DHA in the retina. This study thus provides the reason why DHA is required for visual acuity and may help inform approaches for overcoming retinal disorders associated with DHA deficiency or dysfunction.


DHA; LPAAT3; glycerophospholipid; lysophospholipid acyltransferase; membrane biophysics; membrane lipid; phospholipid turnover; retinal degeneration

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