July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Retina Phosphatidyl Choline Molecular Species Containing DHA and VLC-PUFAs Display Cell-selective Decreases in AdipoR1 Conditional KOs
Author Affiliations & Notes
  • Bokkyoo Jun
    Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana, United States
  • Marie-Audrey Ines Kautzmann
    Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana, United States
  • Khanh Do
    Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana, United States
  • William C Gordon
    Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana, United States
  • Nicolas G Bazan
    Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana, United States
  • Footnotes
    Commercial Relationships   Bokkyoo Jun, None; Marie-Audrey Kautzmann, None; Khanh Do, None; William Gordon, None; Nicolas Bazan, None
  • Footnotes
    Support  NEI EY005121 (NGB) and the EENT Foundation
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2350. doi:
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      Bokkyoo Jun, Marie-Audrey Ines Kautzmann, Khanh Do, William C Gordon, Nicolas G Bazan; Retina Phosphatidyl Choline Molecular Species Containing DHA and VLC-PUFAs Display Cell-selective Decreases in AdipoR1 Conditional KOs. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2350.

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

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Abstract

Purpose : Docosahexaenoic acid (DHA) is necessary for maintenance of retinal health after it is obtained from the diet and delivered through the liver to photoreceptor cells (PR). We have shown that ablation of AdipoR1 leads to selective reduced retinal DHA and PR degeneration (Rice et al, 2015), however, there is incomplete understanding about the role of RPE, PR, and Muller glia (MG) in DHA uptake/retention. DHA is the precursor for Neuroprotectin D1 and of very long chain polyunsaturated fatty acids (VLC-PUFA), which in turn lead to the formation of the pro-homeostatic Elovanoids (ELV). Here, we have studied in detail the DHA lipidome in AdipoR1 RPE, PR, and MG conditional KOs to define key cell specific changes preceding PR dysfunction.

Methods : AdipoR1 conditional knockouts in RPE, PR, and MG were generated with AdipoR1 floxed/floxed mice and mice expressing Cre recombinase, specifically in RPE, PR, and MG. AdipoR1 global KO and wild-type (WT) served as controls. Lipids were extracted from retinas and eyecups (RPE cups) from all genotypes, and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for the identification and quantification of the DHA lipidome.

Results : In the retina of AdipoR1 global KOs DHA and VLC-PUFAs are greatly diminished; however, DHA and VLC-PUFA-containing PC (PC56:12) show trends of reduction in cPR and cMG KOs. For RPE, cMG KO show great reduction in all DHA-containing PCs (PC38:6, PC40:6, PC44:12, PC54:12, PC56:12, and PC58:12). cPR also show reduction in DHA-containing PCs, except for PC38:6. However, cRPE display a slight increase in DHA-containing PCs.

Conclusions : The DHA- and VLC-PUFA-containing PCs are greatly reduced in the RPE, but not in the retina of cMG KO mice, suggesting that DHA regulation in the retina also includes the Muller glia. Whether MG interact with RPE is not clear, but their effect may involve the interphotoreceptor matrix. The fact that the conditional KO of AdipoR1 in one type of cell does not deplete DHA and/or VLC-PUFAs, as shown in the AdipoR1 global KO, suggests that AdipoR1, within several cell types, work together to regulate retinal DHA and VLC-PUFAs.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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