September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Membrane-type Frizzled Related Protein (MFRP) is needed for photoreceptor cell function by retaining docosahexaenoic acid (DHA)
Author Affiliations & Notes
  • Nicolas G Bazan
    Neuroscience Center of Excellence, Louisiana State University Health, New Orleans, Louisiana, United States
  • Bokkyoo Jun
    Neuroscience Center of Excellence, Louisiana State University Health, New Orleans, Louisiana, United States
  • Bo Chang
    The Jackson Laboratory, Bar Harbor, Maine, United States
  • William C Gordon
    Neuroscience Center of Excellence, Louisiana State University Health, New Orleans, Louisiana, United States
  • Footnotes
    Commercial Relationships   Nicolas Bazan, None; Bokkyoo Jun, None; Bo Chang, None; William Gordon, None
  • Footnotes
    Support  NEI grant EY005121, NIGMS grant GM103340, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3178. doi:
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    • Get Citation

      Nicolas G Bazan, Bokkyoo Jun, Bo Chang, William C Gordon; Membrane-type Frizzled Related Protein (MFRP) is needed for photoreceptor cell function by retaining docosahexaenoic acid (DHA). Invest. Ophthalmol. Vis. Sci. 2016;57(12):3178.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Mechanisms for DHA uptake and retention by retinal pigment epithelium (RPE) and photoreceptors involve adiponectin receptor 1 (AdipoR1) and are necessary for photoreceptor function and integrity (Rice et al, Nature Comm, 2015). AdipoR1 KO mice show flecked retinas and selective reduction of DHA in situ and in ex vivo explants and in RPE when incubated with DHA, but arachidonic acid was unchanged. DHA deficiency resulted in absence of long chain polyunsatured fatty acids (VLC-PUFAs, 24-38 carbons) associated with phosphatidylcholine (PC) species. Here we report that the mutant MFRP mice resemble AdipoR1 KO mice, expressing flecked retinas and photoreceptor loss. Here we asked if retinal lipid profiles of mutant MFRP mice show similar changes in DHA-containing VLC-PUFA PCs.

Methods : Lipids were extracted from mutant MFRP and WT mice, and LC-MS/MS lipid species and VLC-PUFAs were identified. Also, retinal sections were imaged by MALDI and DESI mass spectrometry.

Results : Mutant MFRP PCs up to 38C were more abundant than in WT; 38-52C PCs were greatly reduced, but WT PC(38:6) and (40:6) were twice as abundant. PC(32:0), (34:1), (36:4, 2 & 1), (38:6 & 4), & (40:6) were very prominent. Except for PC(44:12), PC42-46C was low in both retinas. PCs from 48-58C (VLC-PUFAs) occurred in WTs, but MFRP PCs were low through 60C. MALDI and DESI imaging showed lipid stratification (PC, PE, or SM) but much less DHA in MFRP.

Conclusions : About 50% of retinal phospholipids are PCs and VLC-PUFA-containing PCs esterified at sn-1, and DHA esterified at the sn-2. The mutant MFRP had no VLC-PUFA PCs, indicating low or no DHA-containing PCs. AdipoR1 regulates DHA levels in RPE and photoreceptors and is required for incorporation of DHA and VLC-PUFA elongation. Molecular organization of phospholipid species and lipid profiles of MFRP mouse retina indicate attenuated DHA uptake and retention, suggesting a faulty molecular switch leads to unavailability of retinal DHA, which leads to photoreceptor loss. MFRP protein may function as a complement to AdipoR1 and/or as an additional necessary mechanism for DHA uptake in membrane molecular organization and in generation of derivatives biosynthesized “on demand” that display pro-homeostatic bioactivity required to sustain RPE-photoreceptor function.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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