Dataset Information

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

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-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.

SUBMITTER: Shindou H

PROVIDER: S-EPMC5519357 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Shindou Hideo H Koso Hideto H Sasaki Junko J Nakanishi Hiroki H Sagara Hiroshi H Nakagawa Koh M KM Takahashi Yoshikazu Y Hishikawa Daisuke D Iizuka-Hishikawa Yoshiko Y Tokumasu Fuyuki F Noguchi Hiroshi H Watanabe Sumiko S Sasaki Takehiko T Shimizu Takao T

The Journal of biological chemistry 20170603 29

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 analys ...[more]

PMID: 28578316

Similar Datasets

Project description:BackgroundRetinoic acid (RA) is important for vertebrate eye morphogenesis and is a regulator of photoreceptor development in the retina. In the zebrafish, RA treatment of postmitotic photoreceptor precursors has been shown to promote the differentiation of rods and red-sensitive cones while inhibiting the differentiation of blue- and UV-sensitive cones. The roles played by RA and its receptors in modifying photoreceptor fate remain to be determined.ResultsTreatment of zebrafish embryos with RA, beginning at the time of retinal progenitor cell proliferation and prior to photoreceptor terminal mitosis, resulted in a significant alteration of rod and cone mosaic patterns, suggesting an increase in the production of rods at the expense of red cones. Quantitative pattern analyses documented increased density of rod photoreceptors and reduced local spacing between rod cells, suggesting rods were appearing in locations normally occupied by cone photoreceptors. Cone densities were correspondingly reduced and cone photoreceptor mosaics displayed expanded and less regular spacing. These results were consistent with replacement of approximately 25% of positions normally occupied by red-sensitive cones, with additional rods. Analysis of embryos from a RA-signaling reporter line determined that multiple retinal cell types, including mitotic cells and differentiating rods and cones, are capable of directly responding to RA. The RA receptors RXR? and RAR?b are expressed in patterns consistent with mediating the effects of RA on photoreceptors. Selective knockdown of RAR?b expression resulted in a reduction in endogenous RA signaling in the retina. Knockdown of RAR?b also caused a reduced production of rods that was not restored by simultaneous treatments with RA.ConclusionsThese data suggest that developing retinal cells have a dynamic sensitivity to RA during retinal neurogenesis. In zebrafish RA may influence the rod vs. cone cell fate decision. The RAR?b receptor mediates the effects of endogenous, as well as exogenous RA, on rod development.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure