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Invest Ophthalmol Vis Sci. 2014 Apr 10;55(5):3150-7. doi: 10.1167/iovs.14-13995.

Effect of reduced retinal VLC-PUFA on rod and cone photoreceptors.

Author information

1
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States.
2
Department of Chemistry, Michigan State University, East Lansing, Michigan, United States.
3
Department of Chemistry, Michigan State University, East Lansing, Michigan, United States Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States.
4
Department of Physiology, Michigan State University, East Lansing, Michigan, United States.
5
Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
6
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.

Abstract

PURPOSE:

Autosomal dominant Stargardt-like macular dystrophy (STGD3) is a juvenile-onset disease that is caused by mutations in Elovl4 (elongation of very long fatty acids-4). The Elovl4 catalyzes the first step in the conversion of C24 and longer fatty acids (FAs) to very long-chain FAs (VLC-FAs, ≥C26). Photoreceptors are particularly rich in VLC polyunsaturated FAs (VLC-PUFA). To explore the role of VLC-PUFAs in photoreceptors, we conditionally deleted Elovl4 in the mouse retina.

METHODS:

Proteins were analyzed by Western blotting and lipids by gas chromatography (GC)-mass spectrometry, GC-flame ionization detection, and tandem mass spectrometry. Retina function was assessed by electroretinography (ERG), and structure was evaluated by bright field, immunofluorescence, and transmission electron microscopy.

RESULTS:

Conditional deletion (KO) of retinal Elovl4 reduced RNA and protein levels by 91% and 96%, respectively. Total retina VLC-PUFAs were reduced by 88% compared to the wild type (WT) levels. Retinal VLC-PUFAs incorporated in phosphatidylcholine were less abundant at 12 months compared to 8-week-old levels. Amplitudes of the ERG a-wave were reduced by 22%, consistent with photoreceptor degeneration (11% loss of photoreceptors). Analysis of the rod a-wave responses gave no evidence of a role for VLC-PUFA in visual transduction. However, there were significant reductions in rod b-wave amplitudes (>30%) that could not be explained by loss of rod photoreceptors. There was no effect of VLC-PUFA reduction on cone ERG responses, and cone density was not different between the WT and KO mice at 12 months of age.

CONCLUSIONS:

The VLC-PUFAs are important for rod, but not cone, function and for rod photoreceptor longevity.

KEYWORDS:

Elovl4; STDG3; VLC-PUFA

PMID:
24722693
PMCID:
PMC4027810
DOI:
10.1167/iovs.14-13995
[Indexed for MEDLINE]
Free PMC Article

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