Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development
Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development
Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs.
- Centre for Eye Research Australia Australia
- National University of Singapore Singapore
- National University of Singapore Libraries Singapore
- Singapore Eye Research Institute Singapore
- Carl Zeiss (Germany) Germany
EXPRESSION, Biochemistry & Molecular Biology, Docosahexaenoic Acids, PERICYTES, Biological Transport, Active, ORGANIZATION, DISEASE, PHAGOCYTOSIS, CLONING, Mice, Animals, Photoreceptor Cells, BRAIN, Mice, Knockout, Science & Technology, 660, Symporters, Optical Imaging, Angiography, Lysophosphatidylcholines, Membrane Transport Proteins, RETINAL-PIGMENT EPITHELIUM, 540, VEGF, Up-Regulation, HEALTH, Microglia, Life Sciences & Biomedicine
EXPRESSION, Biochemistry & Molecular Biology, Docosahexaenoic Acids, PERICYTES, Biological Transport, Active, ORGANIZATION, DISEASE, PHAGOCYTOSIS, CLONING, Mice, Animals, Photoreceptor Cells, BRAIN, Mice, Knockout, Science & Technology, 660, Symporters, Optical Imaging, Angiography, Lysophosphatidylcholines, Membrane Transport Proteins, RETINAL-PIGMENT EPITHELIUM, 540, VEGF, Up-Regulation, HEALTH, Microglia, Life Sciences & Biomedicine
60 Research products, page 1 of 6
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).121 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
