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

  1. Takao Shimizu4
  1. 1 National Center for Global Health and Medicine, and the Univ of Tokyo, Japan;
  2. 2 the University of Tokyo, Japan;
  3. 3 Akita University Graduate School of Medicine, Japan;
  4. 4 National Center for Global Health and Medicine, Japan
  1. ↵* Corresponding author; email: hshindou-tky{at}umin.net

  1. Author contributions: H. Shindou designed the study, performed the experiments, analyzed the data, and wrote the manuscript. H. Koso designed and performed the experiments. H. Sagara performed the electron microscopic experiments. K-M. Nakagawa and H. Noguchi performed the MD simulations. H. Nakanishi performed the lipid analyses. Y. Takahashi maintained the deficient mice, performed experiments and analyzed data. F. Tokumasu supported the DLS analysis. J. Sasaki generated the LPAAT3-KO mice and D. Hishikawa and Y. Iizuka-Hishikawa maintained them. S. Watanabe. and T. Sasaki. designed the study. T. Shimizu designed and wrote the manuscript. All authors assisted in manuscript editing.

Abstract

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-knockout mice. Dynamic light scattering analysis of liposomes and molecular dynamics simulations revealed that the physical characteristics of DHA reduced the membrane-bending rigidity. Following loss of PL-DHA, LPAAT3-knockout mice exhibited abnormalities in the retinal layers, such as incomplete elongation of the outer segment and decreased thickness of the outer nuclear layer, 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.

  • Received April 16, 2017.
  • Accepted June 3, 2017.

This Article

  1. First Published on June 3, 2017 doi: 10.1074/jbc.M117.790568 jbc.M117.790568.
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