Very long-chain fatty acids support synaptic structure and function in the mammalian retina

Blake R. Hopiavuori, Lea D. Bennett, Richard S. Brush, Matthew Van Hook, Wallace B Thoreson, Robert E. Anderson

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Elongation of Very Long chain fatty acids-like 4 (ELOVL4) is a fatty acid elongase responsible for the biosynthesis of very long chain (VLC; ≥ C26) fatty acids in the retina, brain, skin, Meibomian gland, and testes. Heterozygous inheritance of mutant ELOVL4 causes juvenile macular degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3). Retinal photoreceptors are enriched with VLC polyunsaturated fatty acids (VLC-PUFAs), which have been shown by our group and others to be necessary for the survival of rod photoreceptors. Our group performed a series of studies using mice conditionally depleted of retinal Elovl4 (KO) aimed at understanding the role of VLC-PUFAs in long-term retinal health and function, focusing on the role of these fatty acids in mediating synaptic function between the photoreceptors and the rest of the neural retina. The absence of VLC-PUFA from the retina of KO mice resulted in a marked decrease in retinal b-wave responses of the electroretinogram as well as a decrease in the amplitude of the oscillatory potentials mediated by the neural retina. Although there were no measureable differences between KO and wild type (WT) mice in either pre-synaptic rod calcium channel function or post-synaptic bipolar cell glutamate receptor responses, ultrastructural analysis revealed a marked decrease in the diameter of synaptic vesicles in rod terminals. Recent quantification suggests that this decrease in synaptic vesicle size due to the absence of VLC-PUFAs in KO mice, and the consequent decrease in glutamate content, could account for the decrease in b-wave response amplitudes that were previously measured in these animals.

Original languageEnglish (US)
Article numberD113
JournalOCL - Oilseeds and fats, Crops and Lipids
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

very long chain fatty acids
Unsaturated Fatty Acids
rods (retina)
retina
Retina
polyunsaturated fatty acids
Fatty Acids
Synaptic Vesicles
mice
fatty acids
photoreceptors
skin glands
Meibomian Glands
Retinal Rod Photoreceptor Cells
electroretinography
Vertebrate Photoreceptor Cells
calcium channels
Biosynthesis
Glutamate Receptors
Calcium Channels

Keywords

  • ELOVL4
  • Lipids in retinal structure and function
  • Stargardt-like macular dystrophy
  • Very long chain fatty acids
  • Very long chain polyunsaturated fatty acids

ASJC Scopus subject areas

  • Food Science
  • Biochemistry
  • Agronomy and Crop Science

Cite this

Very long-chain fatty acids support synaptic structure and function in the mammalian retina. / Hopiavuori, Blake R.; Bennett, Lea D.; Brush, Richard S.; Van Hook, Matthew; Thoreson, Wallace B; Anderson, Robert E.

In: OCL - Oilseeds and fats, Crops and Lipids, Vol. 23, No. 1, D113, 01.01.2016.

Research output: Contribution to journalReview article

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abstract = "Elongation of Very Long chain fatty acids-like 4 (ELOVL4) is a fatty acid elongase responsible for the biosynthesis of very long chain (VLC; ≥ C26) fatty acids in the retina, brain, skin, Meibomian gland, and testes. Heterozygous inheritance of mutant ELOVL4 causes juvenile macular degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3). Retinal photoreceptors are enriched with VLC polyunsaturated fatty acids (VLC-PUFAs), which have been shown by our group and others to be necessary for the survival of rod photoreceptors. Our group performed a series of studies using mice conditionally depleted of retinal Elovl4 (KO) aimed at understanding the role of VLC-PUFAs in long-term retinal health and function, focusing on the role of these fatty acids in mediating synaptic function between the photoreceptors and the rest of the neural retina. The absence of VLC-PUFA from the retina of KO mice resulted in a marked decrease in retinal b-wave responses of the electroretinogram as well as a decrease in the amplitude of the oscillatory potentials mediated by the neural retina. Although there were no measureable differences between KO and wild type (WT) mice in either pre-synaptic rod calcium channel function or post-synaptic bipolar cell glutamate receptor responses, ultrastructural analysis revealed a marked decrease in the diameter of synaptic vesicles in rod terminals. Recent quantification suggests that this decrease in synaptic vesicle size due to the absence of VLC-PUFAs in KO mice, and the consequent decrease in glutamate content, could account for the decrease in b-wave response amplitudes that were previously measured in these animals.",
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AU - Bennett, Lea D.

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AU - Anderson, Robert E.

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