image: Figure 1. Global gene expression analysis in RPE/choroid of young and aged mice. (A) Pie chart represents the percent of globally expressed transcript subspecies across young (2–3 months, n = 4) and aged (22–24 months, n = 4) mice RPE/choroid from 21,376 annotated transcripts. (B) PCA plots of whole transcriptome data showed distinct clustering of young and aged mice along PC1, which captures the maximum variance (52.4%). Blue and red ellipses indicate young and aged mice and black dots represent the biological replicates (n = 4). (C, D) GO enrichment terms associated with the top 100 PC1 positive loading genes (C) and PC1 negative loading genes (D). (E) MA plot of log2 fold change versus average log counts-per-million (CPM) based on edgeR analysis showing the differential gene expression between aged and young mice RPE/choroid. Red dots indicate differentially expressed genes (FDR ≤0.05), and black dots indicate non-differentially expressed genes. (F) Volcano plot showing genes significantly (p-adj value < 0.05) upregulated (red) and downregulated (blue) in aged mice RPE/choroid. The x-axis represents log2-fold change, and the y-axis represents −log10 (p-value). The dotted line shows a cutoff of −log10 (p-value) < 0.05. Annotated dots represent the top significantly regulated genes. (G) Hierarchical clustering and heatmap analysis of gene expression in the RPE/choroid tissues of the young vs. aged mice. Blue to red represents low to high gene expression.
Credit: Copyright: © 2025 Dubey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“These findings significantly expand our fundamental scientific understanding of age-related retinal diseases while offering potential new biomarkers for clinical diagnosis and therapeutic strategies to reverse biologic aging in the RPE.”
BUFFALO, NY — April 14, 2025 — A new research paper was published in Aging (Aging-US) Volume 17, Issue 3, on March 4, 2025, titled “Deciphering age-related transcriptomic changes in the mouse retinal pigment epithelium.”
The study, led by first authors Sushil K. Dubey and Rashmi Dubey with corresponding author Mark E. Kleinman from East Tennessee State University, reveals that aging causes inflammation, oxidative stress, and gene disruption in the retinal pigment epithelium (RPE), a vital layer of cells in the eye. These changes may explain why older adults are more vulnerable to age-related eye diseases. The researchers also developed a human cell model to study retinal aging and test future therapies.
The RPE plays a key role in maintaining retinal health. It recycles light-sensitive molecules, supports the visual cycle, and protects the retina from damage. When this layer becomes damaged, vision problems such as age-related macular degeneration can develop.
In this study, researchers compared gene activity in RPE cells from young and aged mice. They found that aging increased the activity of genes involved in immune system responses, inflammation, and oxidative stress, three known triggers of tissue damage. At the same time, genes related to vision and light detection became less active, weakening the RPE’s ability to support healthy vision.
To reinforce these findings, the research team also aged human RPE cells in the lab. Over time, these cells showed the same patterns: inflammation increased, while genes tied to visual function decreased. This human cell model offers a practical way to explore how RPE degeneration happens over time and how it might be slowed down or reversed.
The research also identified “hub genes,” which are central players of the gene networks involved in RPE aging. These are connected to immune signaling, oxidative damage, and changes in the eye’s structural support. Many of these genes are already known to be involved in age-related retinal degeneration, so they may become important targets for future treatments aimed at protecting vision in older adults.
“GO annotation of downregulated genes included processes related to visual perception, sensory perception of light stimulus, detection of light stimulus, detection of visible light, detection of external stimulus, detection of abiotic stimulus, phototransduction, cellular response to interferon-beta, response to interferon-beta, and response to light stimulus.”
By mapping how the RPE changes with age at the molecular level, this study provides a clearer understanding of why aging leads to eye disease. It also introduces a reliable laboratory model that researchers can use to test new therapies. Altogether, the work is a key step toward developing treatments to slow or prevent vision loss tied to retinal aging.
Read the full paper: DOI: https://doi.org/10.18632/aging.206219
Corresponding author: Mark E. Kleinman- kleinman@etsu.edu
Keywords: aging, transcriptome, retinal pigment epithelium, oxidative stress, inflammation, chronological aging
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Deciphering age-related transcriptomic changes in the mouse retinal pigment epithelium
Article Publication Date
4-Mar-2025
COI Statement
The authors declare no conflicts of interest related to this study.