June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Acute Dietary Supplementation with Omega-3 Fatty Acid Confers Novel Mechanistic Changes in Retinal Proteome in Mice with Targeted Gene Deletion of Cytochrome P450
Author Affiliations & Notes
  • Caroline Manicam
    Department of Ophthalmology, Universitatsmedizin der Johannes Gutenberg-Universitat Mainz, Mainz, Rheinland-Pfalz, Germany
  • Anna Herfurth
    Department of Ophthalmology, Universitatsmedizin der Johannes Gutenberg-Universitat Mainz, Mainz, Rheinland-Pfalz, Germany
  • Franz Grus
    Department of Ophthalmology, Universitatsmedizin der Johannes Gutenberg-Universitat Mainz, Mainz, Rheinland-Pfalz, Germany
  • Norbert Pfeiffer
    Department of Ophthalmology, Universitatsmedizin der Johannes Gutenberg-Universitat Mainz, Mainz, Rheinland-Pfalz, Germany
  • Natarajan Perumal
    Department of Ophthalmology, Universitatsmedizin der Johannes Gutenberg-Universitat Mainz, Mainz, Rheinland-Pfalz, Germany
  • Footnotes
    Commercial Relationships   Caroline Manicam None; Anna Herfurth None; Franz Grus None; Norbert Pfeiffer None; Natarajan Perumal None
  • Footnotes
    Support  German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) grant (MA 8006/1-1)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2710 – A0074. doi:
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      Caroline Manicam, Anna Herfurth, Franz Grus, Norbert Pfeiffer, Natarajan Perumal; Acute Dietary Supplementation with Omega-3 Fatty Acid Confers Novel Mechanistic Changes in Retinal Proteome in Mice with Targeted Gene Deletion of Cytochrome P450. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2710 – A0074.

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

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Abstract

Purpose : Cytochrome P450 (CYP) gene mutations are a common predisposition associated with glaucoma. Although the molecular mechanisms are largely unknown, omega-3 polyunsaturated fatty acids (ω3) and their CYP-derived bioactive mediators play significant roles in proper maintenance of neurovascular functions and homeostasis in the retina. We tested the hypothesis that acute dietary supplementation with ω3 confers neuro-vasculoprotective effects attributed to inherent lack of the main murine CYP gene (Cyp2c44) in the retina in vivo.

Methods : Male mice with targeted deletion of the Cyp2c44 gene (KO) and their wild type floxed littermates (WT) were subjected to daily oral gavaging for 7 days with 0.01 ml/g ω3 composed of menhaden fish oil. Another group in respective strains served as vehicle-treated controls. Retina was isolated at day 8 post-treatment (n=9/group) and subjected to mass spectrometry (MS)-based proteomics and in-silico bioinformatics analyses.

Results : Proteomics analysis identified a total of 1402 retinal proteins (FDR<1%) and ω3 administration elicited significant (p < 0.05) differential expressions of 56 and 61 proteins in KO and WT mice, respectively. Noteworthy, ω-3 had a profound influence on the regulation of proteins involved in neuronal and mitochondrial activities in WT mice, while significantly improving the retinal metabolic status in the KO mice. The key molecular mechanistic changes conferred by ω3 in the WT retina were implicated in neurotransmission (p=4.22E-3), mitochondrial organization (p=1.62E-2), inhibition of neuronal cell death (p=2.33E-2) and activation of nitric oxide signalling (p=1.39E-2). Remarkably, ω3 supplementation in KO mice resulted in significant changes in the proteins involved in vision functions (p=3.69E-2), heightened metabolic activity via glycolysis (p=2.11E-2) and AMPK signalling pathway (p=2.33E-2), and inhibited apoptosis (p=7.78E-3).

Conclusions : Our findings provide the first in-depth experimental data that support our hypothesis that short-term dietary supplementation with ω3 can provide physiologically relevant beneficial effects in the retina via specific neuro-vasculoprotective signalling mechanisms, particularly by ameliorating retinal bioenergetics in the absence of Cyp2c44. The potential adjunct use of ω3 for glaucoma therapy needs further investigation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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