Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8642
Full metadata record
DC FieldValueLanguage
dc.contributor.authorPerumal, Natarajan-
dc.contributor.authorHerfurth, Anna-
dc.contributor.authorPfeiffer, Norbert-
dc.contributor.authorManicam, Caroline-
dc.date.accessioned2023-01-25T11:37:02Z-
dc.date.available2023-01-25T11:37:02Z-
dc.date.issued2022-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/8658-
dc.description.abstractCytochrome 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.en_GB
dc.description.sponsorshipGefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577de
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleShort-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 deletionen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-8642-
jgu.type.contenttypeScientific articlede
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleCellsde
jgu.journal.volume11de
jgu.journal.issue21de
jgu.pages.alternative3494de
jgu.publisher.year2022-
jgu.publisher.nameMDPIde
jgu.publisher.placeBaselde
jgu.publisher.issn2073-4409de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.3390/cells11213494de
jgu.organisation.rorhttps://ror.org/023b0x485-
jgu.subject.dfgLebenswissenschaftende
Appears in collections:DFG-491381577-G

Files in This Item:
  File Description SizeFormat
Thumbnail
shortterm_omega3_supplementat-20230124121226770.pdf4.38 MBAdobe PDFView/Open