Scientists have found that promoting venom-1 (Prom1) plays a crucial role in maintaining retinal pigment epithelial (RPE) cells (a critical supporter of the retina), and its loss may be a key driver of eye aging. A research team at the Vanderbilt University Medical Center, led by Dr. Sujoy Bhattacharya, studied the situation of PROM1 in mouse RPE cells. Their groundbreaking discoveries are published in cellrevealing new insights on the mechanisms behind RPE degeneration, thus elucidating potential triggers of vision loss.
Studies have long identified its role in the photosensitive cells of the eyes, but its function in retinal pigment epithelial cells remains unclear. Using advanced imaging methods, the researchers allowed scientists to observe the cells in detail and found that Prom1 is present in human and mouse RPE cells and helps maintain normal cellular function. “Our study shows that losing PROM1 function weakens these cells, resulting in similar damage to the age-related macular degeneration, a disease that causes gradual loss of vision,” said Dr. Bhattacharya. The team used specialized techniques to visualize PROM1 in the mitochondria of RPE cells, a tiny structure that produces energy for the cells.
The results show that when Prom1 decreases, retinal pigment epithelial cells deform, and the fluid built under the retina, the photosensitive neuronal cells begin to disappear. It is worth noting that loss of PROM1 triggers a chain reaction that leads to cell death, suggesting that PROM1 helps protect these cells from decomposition. These findings support early studies linking Prom1 gene changes to macular diseases, which are conditions that affect central vision and lead to vision loss.
Dr. Bhattacharya’s team also found that the lack of PROM1 interferes with the unit’s natural cleaning process, called Autophagy, which eliminates damaged components, resulting in pressure and further damage. The study shows that this destruction shares similarities with geographical atrophy, a severe age-related macular degeneration in which cells in the retina are wasted. “By demonstrating that Prom1 loss leads to harmful changes similar to this condition, we show why it is important to find a treatment for this pathway,” explains Dr. Bhattacharya.
In addition to its association with retinal pigment epithelial degeneration, Dr. Bhattacharya also discovered Prom1 in mitochondria, suggesting that it plays a previously unknown role in energy production and cellular health. This discovery opens up new possibilities for understanding new possibilities for metabolic diseases that affect cells to produce energy and are associated with vision loss.
The importance of Dr. Bhattacharya’s research does not go beyond the scope of explanation of the development of macular degeneration. Using mouse models to study human disease in this study provides a valuable tool for testing new therapies designed to protect retinal pigment epithelial cells. Although previous studies using complete prom1 in mice showed rapid vision loss, this study highlights the need to focus on specific cell types to understand the unique role of Prom1 in different parts of the eye.
The findings of Dr. Bhattacharya and colleagues enhance the idea that Prom1 is a key factor in keeping retinal pigment epithelial cells healthy and may lead to new therapeutic strategies for macular degeneration. The researchers stressed that more research is needed to explore how PROM1 interacts with other retinal cell types that cause the disease. By revealing these connections, scientists are getting closer to developing ways to slow down or prevent retinal pigment epithelial cell damage and vision loss.
Dr. Bhattacharya added: “Our study convincingly demonstrates that mouse retinal pigment epithelium (RPE) expresses the in situ prom1 gene, at least at least enough to influence critical RPE processes, including autologous and lysosomal activity to remove waste. Prom1 is the importance of a central driver of cell-autonomous RPE homeostasis and provides promising guidance for therapeutic advances in retinal diseases.”
Journal Reference
Bhattacharya S., Yang TS, Nabit BP, Krystofiak ES, Rex TS, ChaumE. Cell, 2024. doi: https://doi.org/10.3390/cells13211761
About the Author
Sujoy Bhattacharya He is an Assistant Professor of Research at the Vanderbilt University Medical Center for Ophthalmology and Visual Science, and has studied the molecular mechanisms that contribute to atrophic age-related macular degeneration (AAMD). He is a cell biologist through training and has more than 20 years of experience in studying the physiology and pathophysiology of epithelial cells. He is interested in exploring the aging biology that causes RPE dysfunction and impairs retinal health and homeostasis. His work includes studying age-related apoptosis and aging pathways, regulating RPE cell homeostasis, and autophagy through patient-derived inducible pluripotent stem cells (IPSCs), modeling RPE disease, studying mitochondrial bioelements of RPE degeneration, and studying RPE bioelements, and developing novel animal models of AMD.
