"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
