Short-Term Omega-3 Supplementation Modulates Novel Neurovascular and Fatty Acid Metabolic Proteome Changes in the Retina and Ophthalmic Artery of Mice with Targeted Cyp2c44 Gene Deletion

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Abstract
<jats:p>Cytochrome P450 (CYP) gene mutations are a common predisposition associated with glaucoma. Although the molecular mechanisms are largely unknown, omega-3 polyunsaturated fatty acids (ω-3 PUFA) and their CYP-derived bioactive mediators play crucial roles in the ocular system. Here, we elucidated the proteome and cell-signalling alterations attributed to the main human CYP2C gene deficiency using a homologous murine model (Cyp2c44−/−), and unravelled the effects of acute ω-3 PUFA supplementation in two ocular vascular beds comprising the retrobulbar ophthalmic artery (OA) and retina (R). Male Cyp2c44−/− mice (KO) and their floxed littermates (WT) were gavaged daily for 7 days with 0.01 mL/g of ω-3 PUFA composed of menhaden fish oil. Another group in respective strains served as vehicle-treated controls. OA and R were isolated at day 8 post-treatment (n = 9/group) and subjected to mass spectrometry (MS)-based proteomics and in silico bioinformatics analyses. Cyp2c44−/− resulted in significant detrimental proteome changes associated with compromised vascular integrity and degeneration in the OA and R, respectively. However, notable changes in the OA after ω-3 PUFA intake were associated with the maintenance of intercellular junctional and endothelial cell functions, as well as activation of the fatty acid metabolic pathway in the KO mice. Conversely, ω-3 PUFA supplementation profoundly influenced the regulation of a large majority of retinal proteins involved in the preservation of neuronal and phototransduction activities in WT mice, namely synaptophysin, phosducin and guanylate cyclase-1, while significantly abrogating degenerative processes in the KO mice via the regulation of, namely, synaptotagmin-1 and beta-crystallin B2. In gist, this study demonstrated that dietary supplementation with ω-3 PUFA for a short period of seven days regulated specific neuro-vasculoprotective mechanisms to preserve the functionality of the OA and R in the absence of Cyp2c44. The potential adjunct use of ω-3 PUFA for glaucoma therapy needs further investigation.</jats:p>
Autoren
  • Natarajan Perumal
  • Anna Herfurth
  • Norbert Pfeiffer
  • Caroline Manicam
DOI
10.3390/cells11213494
eISSN
2073-4409
Ausgabe der Veröffentlichung
21
Zeitschrift
Cells
Sprache
en
Online publication date
2022
Paginierung
3494 - 3494
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/cells11213494
Datum der Datenerfassung
2022
Titel
Short-Term Omega-3 Supplementation Modulates Novel Neurovascular and Fatty Acid Metabolic Proteome Changes in the Retina and Ophthalmic Artery of Mice with Targeted Cyp2c44 Gene Deletion
Ausgabe der Zeitschrift
11

Datenquelle: Crossref

Andere Metadatenquellen:
Author's licence
CC-BY
Autoren
  • Natarajan Perumal
  • Anna Herfurth
  • Norbert Pfeiffer
  • Caroline Manicam
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.3390/cells11213494
Funding acknowledgements
  • Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577
File(s) embargoed
false
Open access
true
ISSN
2073-4409
Ausgabe der Veröffentlichung
21
Zeitschrift
Cells
Schlüsselwörter
  • 610 Medizin
  • 610 Medical sciences
Sprache
eng
Open access status
Open Access
Paginierung
3494
Datum der Veröffentlichung
2022
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/8658
Herausgeber
MDPI
Datum der Datenerfassung
2023
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Zugang
Public
Titel
Short-term omega-3 supplementation modulates novel neurovascular and fatty acid metabolic proteome changes in the retina and ophthalmic artery of mice with targeted Cyp2c44 gene deletion
Ausgabe der Zeitschrift
11

Files

shortterm_omega3_supplementat-20230124121226770.pdf

Datenquelle: OPENSCIENCE.UB

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