Aging Differentially Remodels the Retina and RPE/Choroid Proteome and Metabolism
Aging significantly alters the proteome of the retina and RPE/Cho in mice, which may have implications for understanding age-related macular degeneration.
Where it sits
this study against the rest of the glutathione (gsh) corpusSummary and findings
The study measured changes in the proteome and metabolic pathways of the retina and retinal pigment epithelium/choroid (RPE/Cho) in young (8-week) and old (73-week) C57BL/6J mice. Aging altered the expression of 85 retinal proteins and 272 RPE/Cho proteins. Not reported in abstract.
Abstract
<h4>Purpose: </h4> The neural retina and retinal pigment epithelium/choroid (RPE/Cho) are metabolically coupled. Metabolic dysfunction of the RPE/Cho contributes to photoreceptor death in age-related macular degeneration (AMD). This study aimed to determine how aging, a major risk factor for AMD, alters the proteome and metabolic pathways in the retina and RPE/Cho. <h4>Methods:</h4> We performed quantitative proteomics on neural retina and RPE/Cho from young (8-week) and old (73-week) C57BL/6J mice. The differentially expressed proteins between old and young, as well as between the retina and RPE/Cho, were visualized using volcano plots and heatmaps, and functional analyses were assessed by Gene Ontology enrichment tools. <h4>Results:</h4> Aging altered the expression of 85 retinal proteins and 272 RPE/Cho, with 16 shared between tissues. In the aged retina, proteins associated with NADP(H) metabolism, neurodegeneration, and immunity were mostly upregulated, while proteins in lipid metabolism, transcription, and epigenetic regulation decreased. In the aged RPE/Cho, all 21 significantly altered lysosomal enzymes and transport proteins increased, together with complement components, and photoreceptor outer segment proteins. These changes accompanied increases in proteins associated with lipid metabolism and protection against lipid peroxidation, while several glutathione metabolism enzymes decreased. Seven shared proteins involved in lipid and NADP(H) metabolism, changed in opposite directions between retina and RPE/Cho. Comparison of the retinal and RPE/Cho proteomes identified 3073 differentially abundant proteins, of which 2452 maintained tissue-specific differences across both age groups, while approximately 17% showed age-dependent shifts in tissue enrichment. These shifts involved proteins associated with metabolism, extracellular matrix, visual function, lysosomal pathways, and innate immunity. Within the metabolic proteome, several glycolytic and fatty acid oxidation proteins showed greater relative enrichment in RPE/Cho with age, whereas glucose transporters and mitochondrial complexes shifted toward the retina. <h4>Conclusions:</h4> Overall, these findings show that aging differentially remodels the retina and RPE/Cho proteome, accompanied by altered metabolic specialization between the two tissues.
Background
This paper investigates the impact of aging on the proteome and metabolic pathways of the retina and RPE/Cho, which are crucial for visual function and are implicated in age-related macular degeneration (AMD). Prior research has established that metabolic dysfunction in these tissues contributes to photoreceptor death in AMD, but the specific proteomic changes associated with aging were not well characterized. Understanding these changes is essential for elucidating the mechanisms underlying AMD and potential therapeutic targets.
Methods
The study utilized quantitative proteomics to analyze neural retina and RPE/Cho samples from young (8-week) and old (73-week) C57BL/6J mice. The sample size (n) is not reported in the abstract. The primary outcome measures included differentially expressed proteins between age groups and between the two tissues, visualized using volcano plots and heatmaps.
Results
Aging altered the expression of 85 retinal proteins and 272 RPE/Cho proteins, with 16 proteins shared between the two tissues. Specific findings include upregulation of proteins associated with NADP(H) metabolism and neurodegeneration in the aged retina, while proteins in lipid metabolism decreased. In the aged RPE/Cho, all 21 significantly altered lysosomal enzymes and transport proteins increased, alongside changes in lipid metabolism proteins. Approximately 17% of proteins showed age-dependent shifts in tissue enrichment.
Interpretation
These findings indicate significant proteomic changes with aging that may contribute to the pathophysiology of AMD. While the results are statistically significant, the clinical relevance remains uncertain as the study does not directly link these proteomic changes to functional outcomes or disease progression. The reliance on a rodent model and the absence of human data limit the applicability of these findings to clinical practice.
Key findings
- Aging altered the expression of 85 retinal proteins and 272 RPE/Cho proteins.
- In the aged retina, proteins associated with NADP(H) metabolism, neurodegeneration, and immunity were mostly upregulated.
- In the aged RPE/Cho, all 21 significantly altered lysosomal enzymes and transport proteins increased.
- Approximately 17% of proteins showed age-dependent shifts in tissue enrichment.
- 3073 differentially abundant proteins were identified, with 2452 maintaining tissue-specific differences across both age groups.
Limitations
- Rodent model may not fully translate to human aging.
- Sample size (n) is not reported in abstract.
- Findings based on protein expression changes without direct functional outcomes.