Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice
Data files
Sep 24, 2025 version files 13.80 MB
-
FPKM_12movs18mo_Elovl2.txt
10.86 MB
-
POS_lipidomics_245_supp-4w.csv
135.02 KB
-
POS_lipidomics_245_supp-5d.csv
302.88 KB
-
POS_lipidomics_245_supp-9w.csv
176.46 KB
-
RAWCOUNTS_18mo_VEHvsSUPPL.txt
1.87 MB
-
README.md
16.57 KB
-
retina_lipidomics_3mo_vs_18mo.csv
71.23 KB
-
retina_lipidomics_Elovl2-2-M.csv
68.56 KB
-
retina_lipidomics_Elovl2-3-F.csv
58.39 KB
-
retina_lipidomics_Elovl2.csv
56.31 KB
-
retina_proteins_quantification_3mo_vs_18mo.csv
6.71 KB
-
retina_tFA_Elovl2.csv
3.31 KB
-
retina_tFA-different_age_stages.csv
8.55 KB
-
ROS_lipidomics_3mo_vs_18mo.csv
163.38 KB
Abstract
The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), primarily localized in cell membranes, where they govern membrane biophysical properties. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, which is associated with normal age-related reductions in contrast sensitivity, diminished photoreceptor function and delayed rod-mediated dark adaptation recovery, 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. The methylation status of the ELOVL2 promoter is currently one of the best predictors of chronological age. Here, we show that lower VLC-PUFA abundance in the aged mouse retina is accompanied by a reduction in visual function. Similarly, mice lacking ELOVL2-specific enzymatic activity (Elovl2C234W) demonstrate reduced contrast sensitivity and slower rod-mediated dark adaptation. Intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals improved visual function for up to 4 weeks and reduced accumulation of ApoE- and C3d-positive sub-RPE deposits. The gene expression pattern observed in supplemented retinas exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature resembling younger retinas. Finally, we present human genetic data from the IAMGDC and UK Biobank showing an association of two variants in the ELOVL2 locus with the onset of intermediate AMD, underlining the translational importance of our findings. Our work highlights VLC-PUFA supplementation as potential therapeutic opportunity and defines ELOVL2 as a promising target for interventions to prevent age-related vision loss.
Dataset DOI: 10.5061/dryad.gxd25480h
Description of the data and file structure
To investigate molecular changes retinas in aging and after lipid supplementation, total fatty acid, global lipidomic, transcriptomic, and targeted proteomic analyses were performed on mouse retinas and photoreceptor outer segments. The data in this file was used to produce panels in Figure 1, 3, 5 and 6 and Supplementary Figure 1, 3, 5 and 6 of the associated publication. In the associated publication, we utilized p-values from the multiple t test or 2-way ANOVA. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Files and variables
File: retina_tFA-different_age_stages.csv
Description: Total fatty acid analysis was performed on mouse retinas collected from different age stages. The data in this file was used to produce panels in Figure 1 of the associated publication. The statistical analysis was performed by utilizing 2-way ANOVA. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- FAs: Names of the fatty acids detected in the analysis.
- Chemical formula: Molecular formula of each fatty acid.
- m/z: Mass-to-charge ratio of the detected fatty acid ion.
tR/min: Retention time in minutes during chromatographic separation.
Sample Columns
- Columns labeled by age group and replicate (e.g., 3mo-1, 3mo-2, …, 23mo-5) represent fatty acid abundances measured from mouse retinas at specific ages:
- 3mo: 3 months old
- 6mo: 6 months old
- 12mo: 12 months old
- 18mo: 18 months old
- 23mo: 23 months old
The suffix (e.g., -1, -2, -3, etc.) indicates biological replicates within each age group
Missing values "0" indicate not detected species
File: retina_tFA_Elovl2.csv
Description: To investigate molecular changes in Elovl2 mouse, total fatty acid analysis was performed on mouse retinas collected from age matched wild type and Elovl2 mutant mice. The data in this file was used to produce panels in Figure 3 of the associated publication. In the associated publication, we utilized p-values from the multiple t test . This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- FAs: Names of the fatty acids detected in the analysis.
- Chemical formula: Molecular formula of each fatty acid.
- m/z: Mass-to-charge ratio of the detected fatty acid ion.
- tR/min: Retention time in minutes during chromatographic separation.
Sample Columns
- WT1–WT4: Biological replicates from wild-type mouse retinas.
- Elovl2_1–Elovl2_4: Biological replicates from Elovl2 knockout mouse retinas.
File: retina_lipidomics_3mo_vs_18mo.csv
Description: To investigate molecular changes retinas in aging, global lipidomic analysis was performed on mouse retinas collected from 3-month-old and 18-month-old mice. The data in this file was used to produce panels in Figure 1 and Supplementary Figure 1 of the associated publication. In the associated publication, we utilized p-values from the multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis.
- Class: Lipid class each molecule belongs to.
- Formula: Molecular formula of each lipid.
- BaseRt: Retention time at which the lipid elutes during chromatographic separation.
Sample Columns
- 3mo-1 to 3mo-5: Biological replicates from mouse retinas collected at 3 months of age.
- 18mo-1 to 18mo-5: Biological replicates from mouse retinas collected at 18 months of age.
File: retina_lipidomics_Elovl2.csv
Description: To investigate molecular changes in Elovl2 mouse, global lipidomic analysis was performed on mouse retinas collected from age matched wild type and Elovl2 mutant mice. The data in this file was used to produce panels in Figure 3 and Supplementary Figure 3 of the associated publication. In the associated publication, we utilized p-values from the multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis.
- Class: Lipid class each molecule belongs to (e.g., phospholipids, sphingolipids).
- Formula: Molecular formula of each lipid.
- BaseRt: Retention time at which the lipid elutes during chromatographic separation.
Sample Columns
- WT1–WT3: Biological replicates from wild-type mouse retinas.
- Elovl2_1–Elovl2_2: Biological replicates from Elovl2 knockout mouse retinas.
File: retina_lipidomics_Elovl2-2-M.csv
Description: To investigate molecular changes in Elovl2 mouse, global lipidomic analysis was performed on mouse retinas collected from age matched wild type and Elovl2 mutant male mice. The data in this file was used to produce panels in Figure 3 and Supplementary Figure 3 of the associated publication. In the associated publication, we utilized p-values from the multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis.
- Class: Lipid class each molecule belongs to (e.g., phospholipids, sphingolipids).
- Formula: Molecular formula of each lipid.
- BaseRt: Retention time at which the lipid elutes during chromatographic separation.
Sample Columns
- WT1–WT4: Biological replicates from wild-type mouse retinas.
- Elovl2_1–Elovl2_2: Biological replicates from Elovl2 knockout mouse retinas.
File: retina_lipidomics_Elovl2-3-F.csv
Description: To investigate molecular changes in Elovl2 mouse, global lipidomic analysis was performed on mouse retinas collected from age matched wild type and Elovl2 mutant female mice. The data in this file was used to produce panels in Figure 3 and Supplementary Figure 3 of the associated publication. In the associated publication, we utilized p-values from the multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis.
- Class: Lipid class each molecule belongs to (e.g., phospholipids, sphingolipids).
- Formula: Molecular formula of each lipid.
- BaseRt: Retention time at which the lipid elutes during chromatographic separation.
Sample Columns
- WT1–WT2: Biological replicates from wild-type mouse retinas.
- Elovl2_1–Elovl2_3: Biological replicates from Elovl2 knockout mouse retinas.
File: POS_lipidomics_245_supp-5d.csv
Description: To investigate molecular changes retinas after lipid supplementation, global lipidomics was performed on mouse photoreceptor outer segments isolated from retina receiving vehicle and 24:5 supplementation 5 days post injection. The data in this file was used to produce panels in Figure 5 and Supplementary Figure 5 of the associated publication. In the associated publication, we utilized p-values from the multiple t test . This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis.
- Class: Lipid class each molecule belongs to (e.g., phospholipids, sphingolipids).
- Formula: Molecular formula of each lipid.
- BaseRt: Retention time at which the lipid elutes during chromatographic separation.
- MainIon: The primary ion (mass-to-charge signal) detected for the lipid species.
Sample Columns
- veh_G45, veh_G47, veh_105M, veh_105F: Vehicle-treated samples from different groups/conditions, with replicate numbers indicated by the suffix (e.g., veh_G45_1, veh_G45_2).
- 24:5_G47, 24:5_105M, 24:5_105F, 24:5_G45: Samples treated with fatty acid 24:5 in the respective groups/conditions, with replicate numbers indicated by the suffix.
File: POS_lipidomics_245_supp-4w.csv
Description: To investigate molecular changes retinas after lipid supplementation, global lipidomics was performed on mouse photoreceptor outer segments isolated from retina receiving vehicle and 24:5 supplementation 4 weeks post injection. The data in this file was used to produce panels in Figure 6 of the associated publication. In the associated publication, we utilized p-values from the multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis (prefix “VEH” indicates vehicle dataset).
- Class: Lipid class each molecule belongs to (e.g., phospholipids, sphingolipids).
- Formula: Molecular formula of each lipid.
- Base245_t: Retention time at which the lipid elutes during chromatographic separation.
Sample Columns
- VEH_2, VEH_4, VEH_5, VEH_6, VEH_7, VEH_8: Vehicle-treated samples, with replicate numbers indicated by the suffix.
- 245_2, 245_4, 245_5, 245_6, 245_7, 245_8: Samples treated with compound 245, with replicate numbers indicated by the suffix.
File: POS_lipidomics_245_supp-9w.csv
Description: To investigate molecular changes retinas after lipid supplementation, global lipidomics was performed on mouse photoreceptor outer segments isolated from retina receiving vehicle and 24:5 supplementation 9 weeks post injection. The data in this file was used to produce panels in Figure 6 of the associated publication. In the associated publication, we utilized p-values from the multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis.
- Class: Lipid class each molecule belongs to (e.g., phospholipids, sphingolipids).
- Calc Mass: Calculated monoisotopic mass of the lipid molecule.
- Formula: Molecular formula of each lipid.
- BaseRt: Retention time at which the lipid elutes during chromatographic separation.
- MainIon: Primary ion (mass-to-charge signal) detected for the lipid species.
Sample Columns
- VEH2, VEH3, VEH4, VEH5, VEH6, VEH7, VEH10: Vehicle-treated samples, with replicate numbers indicated by the suffix.
- 245_2, 245_3, 245_4, 245_5, 245_6, 245_7, 245_10: Samples treated with compound 245, with replicate numbers indicated by the suffix.
File: ROS_lipidomics_3mo_vs_18mo.csv
Description: To investigate molecular changes retinas in aging, global lipidomic analysis was performed on photoreceptor outer segments isolated from retinas collected from 3-month-old and 18-month-old mice. The data in this file was used to produce panels in Figure 1 and Supplementary Figure 1 of the associated publication. In the associated publication, we utilized p-values from the multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- LipidMolec: Names of the lipid molecules detected in the analysis.
- Class: Lipid class each molecule belongs to (e.g., phospholipids, sphingolipids).
- Formula: Molecular formula of each lipid.
- BaseRt: Retention time at which the lipid elutes during chromatographic separation.
Sample Columns
- 3mo-1 to 3mo-10: Biological replicates from mouse retinas collected at 3 months of age (10 replicates total).
- 18mo-1 to 18mo-10: Biological replicates from mouse retinas collected at 18 months of age (10 replicates total).
File: retina_proteins_quantification_3mo_vs_18mo.csv
Description: To address whether age-related visual decline involves changes in the phototransduction cascade, we quantified proteins involved in signal transduction in POS, (Rho, Pde6a, Pde6b, Gnat1 and Gbb1) in retinas collected from 3-month-old and 18-month-old mouse using a stable isotope-labeled (SIL) peptides-based absolute quantification method. The data in this file was used to produce panels in Figure 1 and Supplementary Figure 1 of the associated publication. The statistical analysis was performed by utilizing multiple t test. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- IS: Stable isotope–labeled (SIL) peptides used as internal standards for quantification of PDE6A, PDE6B, GNAT1, GBB and Rho.
- sample: Biological sample from 3-month-old and 18-month-old mice which protein-derived peptides were quantified.
- Area-peptide: Peak area corresponding to the endogenous (unlabeled) peptide.
- Area-IS: Peak area corresponding to the SIL internal standard peptide.
- IS conc (mg/mL): Concentration of the internal standard stock solution in mg/mL.
- MW: Molecular weight of the peptide.
- purity: Chemical purity of the SIL peptide.
- dilution: Dilution factor applied to the internal standard solution.
- IS volume/µL: Volume of internal standard solution added to the sample (in µL).
- IS conc (mol): Final molar concentration of the internal standard in the assay.
- peptide (mol): Calculated molar amount of the endogenous peptide in the sample.
File: FPKM_12movs18mo_Elovl2.txt
Description: Bulk RNAsequencing analysis was performed on mouse retinas collected from different age stages and genotypes. The data in this file was used to produce panels in Figure 3 of the associated publication. Differential expression analysis was performed using DESeq2. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- gene_id: Unique identifier for each gene.
- WT1_12mo, WT2_12mo, WT3_12mo: Biological replicates from wild-type mouse retinas at 12 months of age.
- Mut1_12mo, Mut2_12mo, Mut3_12mo: Biological replicates from mutant mouse retinas at 12 months of age.
- WT1_18mo, WT2_18mo, WT3_18mo, WT4_18mo: Biological replicates from wild-type mouse retinas at 18 months of age.
- gene_name: Standard gene symbol.
- gene_chr: Chromosome location of the gene.
- gene_start: Start coordinate of the gene on the chromosome.
- gene_end: End coordinate of the gene on the chromosome.
File: RAWCOUNTS_18mo_VEHvsSUPPL.txt
Description: Bulk RNAsequencing analysis was performed on vehicle- and 24:5-supplemented mouse retinas. The data in this file was used to produce panels in Figure 5 of the associated publication. Differential expression analysis was performed using DESeq2. This file can be opened with any text editing software. In the present study, this file was included in analyses that utilized the Prism software.
Variables
- neid: Unique identifier for each gene or feature measured (depending on the dataset context).
- 18mo_supp_1, 18mo_supp_2, 18mo_supp_3: Biological replicates from 18-month-old mice in the supplemented group.
- 18mo_veh_1, 18mo_veh_2, 18mo_veh_3: Biological replicates from 18-month-old mice in the vehicle-treated group.
Code/software
The software was used for statistical analysis and generating figures is Prism 10, Version 10.1.2 (324)
Access information
Other publicly accessible locations of the data:
- Bulk RNA-sequencing data generated in this study have been deposited in the NCBI Gene Expression Omnibus (GEO) under accession number GSE303302.
- snRNA-sequencing data generated in this study have been deposited under accession number GSE303793.
- The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD066430
Data was derived from the following sources:
- International AMD Genomics Consortium (IAMGDC, n=2,407, mean age at diagnosis: 74.1 years)
- Incident AMD cases from the UK Biobank (n=1,309, mean age of onset: 62.8 years)