PXD066430-1

PXD066430 is an original dataset announced via ProteomeXchange.

Title	Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Restoration of Vision in Aging
Description	The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD). ELOVL2 (Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently one of the best predictors of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2C234W) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Short-term and long-term intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals significantly improved visual function and reduced accumulation of ApoE and C3d in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature of younger retina. Finally, we present the first human genetic data showing significant association of two variants in the ELOVL2 locus with the onset of intermediate AMD, underlying the translational significance of our findings. In sum, our study identifies novel therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.
HostingRepository	PRIDE
AnnounceDate	2025-11-02
AnnouncementXML	Submission_2025-11-01_22:25:48.833.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fangyuan Gao
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-22 17:08:29	ID requested
⏵ 1	2025-11-01 22:25:49	announced

10.1126/scitranslmed.ads5769;

Gao F, Tom E, Rydz C, Cho W, Kolesnikov AV, Sha Y, Papadam A, Jafari S, Joseph A, Ahanchi A, Balalaei Someh Saraei N, Lyon DC, Foik A, Nie Q, Grassmann F, Kefalov VJ, Skowronska-Krawczyk D, Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice. Sci Transl Med, 17(817):eads5769(2025) [pubmed]

submitter keyword: VLC-PUFA, lipid supplementation,PUFA, AMD, ELOVL2, aging

Skowronska-Krawczyk, Dorota
contact affiliation	1. Gavin Herbert Eye Institute - Center for Translational Vision Research, Department of Ophthalmology, University of California Irvine, CA, 92697, USA 2. Department of Physiology and Biophysics, School of Medicine, University of California Irvine, CA
contact email	dorotask@hs.uci.edu
lab head
Fangyuan Gao
contact affiliation	University of California, Irvine
contact email	fangyuag@hs.uci.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD066430

PRIDE project URI

• PRIDE
  1. PXD066430
     1. Label: PRIDE project
     2. Name: Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Restoration of Vision in Aging