Scientists have discovered that Prominin-1 (Prom1) plays a vital role in maintaining retinal pigment epithelial (RPE) cells—critical supporters of the retina—healthy, and its loss may be a key driver of vision decline in aging eyes. A research team at Vanderbilt University Medical Center, led by Dr. Sujoy Bhattacharya, investigated what happens when Prom1 is reduced in RPE cells in mice. Their groundbreaking findings, published in Cells, reveal new insights into the mechanisms behind RPE degeneration, shedding light on a potential trigger for vision loss.
Research has long recognized Prom1 for its role in light-sensitive cells of the eye, but its function in retinal pigment epithelial cells has remained unclear. Using advanced imaging methods, which allow scientists to see cells in great detail, the researchers found that Prom1 is present in both human and mouse RPE cells and helps maintain normal cell function. “Our study shows that losing Prom1 function weakens these cells, leading to damage similar to that seen in dry age-related macular degeneration, a condition that causes gradual vision loss,” said Dr. Bhattacharya. The team used specialized techniques to visualize Prom1 in the mitochondria of RPE cells, the tiny structures that produce energy for the cell.
Results showed that when Prom1 was reduced, retinal pigment epithelial cells became misshaped, fluid built under the retina, and light-sensitive neuronal cells started to die off. Notably, the loss of Prom1 set off a chain reaction leading to cell death, showing that Prom1 helps protect these cells from breaking down. These findings support earlier studies that linked Prom1 gene changes to macular diseases, which are conditions affecting central vision and causing vision loss.
Dr. Bhattacharya’s team also found that a lack of Prom1 interfered with the cell’s natural cleanup process, called autophagy, which removes damaged components, leading to stress and further damage. The study showed that this disruption shared similarities with geographic atrophy, a severe form of dry age-related macular degeneration where cells in the retina waste away. “By proving that Prom1 loss leads to harmful changes similar to this condition, we show why it is important to find treatments that target this pathway,” explained Dr. Bhattacharya.
Beyond its connection to retinal pigment epithelial degeneration, Dr. Bhattacharya found Prom1 inside mitochondria, suggesting it plays a previously unknown role in energy production and cell health. This discovery opens new possibilities for understanding metabolic disorders, which are conditions that affect how cells generate energy and are related to vision loss.
The importance of Dr. Bhattacharya’s study goes beyond explaining how macular degeneration develops. Using a mouse model to study human diseases in this research provides a valuable tool for testing new treatments designed to protect retinal pigment epithelial cells. While previous research using complete Prom1 removal in mice showed quick vision loss, this study highlights the need to focus on specific cell types to understand Prom1’s distinct roles in different parts of the eye.
Dr. Bhattacharya and colleague’s findings strengthen the idea that Prom1 is a key factor in keeping retinal pigment epithelial cells healthy and may lead to new treatment strategies for macular degeneration. The researchers stress that more studies are needed to explore how Prom1 interacts with other retinal cell types that contribute to the disease. By uncovering these links, scientists are moving closer to developing ways to slow or prevent retinal pigment epithelial cell damage and vision loss.
Dr. Bhattacharya added: “Our studies convincingly show that mouse retinal pigment epithelium (RPE) expresses the Prom1 gene in situ, at least to a sufficient level, to impact key RPE processes, including waste removal by autophagy and lysosomal activity. We found that loss of Prom1 inhibits autophagy and promotes epithelial-mesenchymal transition in mouse RPE cells. Our findings also highlight the importance of Prom1 as a central driver of cell-autonomous RPE homeostasis and offer promising directions for therapeutic advancements in retinal diseases.”
Journal Reference
Bhattacharya S., Yang T.S., Nabit B.P., Krystofiak E.S., Rex T.S., Chaum E. “Prominin-1 Knockdown Causes Retinal Pigment Epithelial Degeneration in a Mouse Model.” Cells, 2024. DOI: https://doi.org/10.3390/cells13211761
About the Author
Sujoy Bhattacharya is a Research Assistant Professor of Ophthalmology and Visual Sciences at the Vanderbilt University Medical Center, studying the molecular mechanisms contributing to RPE degeneration in atrophic age-related macular degeneration (aAMD). He is a cell biologist by training and has more than 20 years of experience studying the physiology and pathophysiology of epithelial cells. He is interested in exploring the biology of aging that contributes to RPE dysfunction and impairs retinal health and homeostasis. His work includes studying age-related apoptotic and senescence pathways, regulating RPE cell homeostasis and degeneration through autophagy, RPE disease modeling with patient-derived induced pluripotent stem cells (iPSCs), investigating mitochondrial bioenergetics in RPE degeneration, and developing novel animal models of aAMD.
