Plasma metabolomes of aged rhesus macaques with and without maculopathies
Data files
May 28, 2026 version files 659.87 KB
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NHPPDDrusen.xlsx
655.84 KB
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README.md
4.03 KB
Abstract
Mitochondrial dysfunction is associated with aging and age-related macular degeneration (AMD), but human studies have limited access to ocular tissues, and mouse models do not recapitulate AMD features such as drusen. Nonhuman primates (NHPs) exhibit long lifespans, a true macula, and AMD-related phenotypes, including punctate dots composed of intracellular lipid droplets and soft drusen composed of extracellular deposits beneath the retinal pigment epithelium (RPE). In this study, we perform a comprehensive quantitative analysis of mitochondrial ultrastructure, complemented by functional imaging, plasma metabolomics, and genetic data implicating mitochondrial dysfunction in the RPE of aged rhesus macaques with AMD phenotypes. Retinal flavoprotein fluorescence imaging of NHP drusen showed increased heterogeneity similar to AMD patients. Quantitative morphometric profiling of RPE mitochondria revealed (1) concentric cristae and type I paracrystalline inclusions indicating early stress in normal aging, (2) hyperbranching, fusion, and megamitochondria formation indicating adaptive remodeling with punctate lesions, and (3) reduced fusion, sparse branching, and compromised ultrastructure reflecting mitochondrial degeneration in eyes with soft drusen. Plasma metabolomics showed elevated glycolytic and tricarboxylic acid cycle ratios, higher sphinganine-1-phosphate levels, and reduced thiol redox buffering that reflect metabolic strain in animals with punctate dots, and decreased methionine sulfone/methionine, 2-hydroxybutanoic acid, and increased 3-hydroxybutyrate/glucose ratios, indicating chronic mitochondrial decline in animals with drusen. Whole exome sequencing of mitochondrial genes identified a single nucleotide variant MT:9582G>A in the cytochrome-c oxidase subunit III (COX3) gene associated with NHP drusen. Our data suggest that in macaques, punctate dots may reflect an adaptive mitochondrial trajectory, while soft drusen are characterized by failed RPE remodeling and degeneration, providing insights into mitochondrial dysfunction in NHP models of AMD.
Dataset Description
This dataset contains metabolomic and phenotypic data from nonhuman primates (NHPs) evaluated for punctate dots (PD), drusen, and related retinal findings. The spreadsheet includes demographic information, study group assignments, and quantified metabolite/lipid species measurements.
The uploaded file:
- File name:
NHPPDDrusen.xlsx - Worksheet:
NHP PD vs drusen data for Prof.
Each row represents an individual study subject/sample. Columns include subject identifiers, demographic variables, study group labels, and metabolomic features.
Column Descriptions
| Column Name | Description | Units / Scale |
|---|---|---|
| MMU | Unique nonhuman primate subject identifier | Categorical identifier |
| Age | Age of the subject at sample collection | Years |
| Sex | Biological sex of the subject | Categorical (e.g., Male/Female) |
| Group | Experimental or disease classification group | Categorical |
| Label | Additional study label or subgroup annotation | Categorical |
Metabolomic / Lipidomic Variables
The remaining columns primarily represent quantified metabolite and lipid species measured using metabolomic/lipidomic profiling.
Examples include:
CAR 14:1CE 18:2Cer 42:1;O2|Cer 18:1;O2/24:0DG 36:3|DG 18:1_18:2LPC 18:0NAE 9:0
Naming Convention
Lipid/metabolite column names follow standard lipidomics nomenclature conventions:
| Prefix | Description |
|---|---|
| CAR | Acylcarnitines |
| CE | Cholesteryl esters |
| Cer | Ceramides |
| DG | Diacylglycerols |
| Hex3Cer | Trihexosylceramides |
| LPC | Lysophosphatidylcholines |
| NAE | N-acylethanolamines |
| PC | Phosphatidylcholines |
| PE | Phosphatidylethanolamines |
| SM | Sphingomyelins |
| TG | Triacylglycerols |
Numbers separated by colons indicate carbon chain length and degree of unsaturation.
For example:
18:1= 18 carbons and 1 double bond42:2= 42 total carbons and 2 double bonds
Additional annotations may indicate:
- Hydroxylation states (
O2,O3, etc.) - Specific fatty acyl chain composition
- Alternative structural assignments separated by
|
Measurement Values
Metabolomic variables are reported as relative abundance or normalized signal intensity values generated from the lipidomics/metabolomics platform used in the study.
Units may depend on the preprocessing pipeline and analytical platform. Users should refer to the associated manuscript or analytical methods documentation for details regarding:
- Sample preparation
- Instrument platform
- Normalization procedures
- Batch correction methods
- Scaling or transformation procedures
Missing Data
Blank cells or missing values indicate measurements that were unavailable, below detection threshold, or excluded during quality control.
Recommended Use
This dataset is intended for:
- Comparative metabolomic analyses between retinal phenotypes
- Biomarker discovery
- Lipid pathway analysis
- Multivariate statistical modeling
- Correlation with retinal imaging or clinical phenotypes
Users are encouraged to perform appropriate normalization, transformation, and multiple comparison correction during downstream analyses.
Notes
- Subject identifiers have been de-identified.
- Categorical group definitions should be interpreted in the context of the associated study protocol and manuscript.
- Lipid annotations follow standard lipidomics reporting conventions commonly used in mass spectrometry-based analyses.