ARPE-19 cells are a laboratory-grown cell line widely used in scientific research. These cells are valuable for investigating the human eye, serving as a consistent model system for studying its biology. They replicate characteristics of eye cells, making them useful for various experimental applications. Researchers use ARPE-19 cells to gain insights into ocular health and disease mechanisms.
What Are ARPE-19 Cells
ARPE-19 cells are a cell line derived from the human retinal pigment epithelium (RPE). The RPE is a layer of cells located at the back of the eye, between the light-sensing photoreceptors and the choroid, which supplies blood. This specific cell line originated spontaneously in 1986 from the normal eyes of a 19-year-old male who died from head trauma.
These cells are considered an “immortalized” cell line, meaning they can divide indefinitely in a laboratory. This makes them a stable resource for long-term studies, unlike primary cells with limited lifespan. When cultured, ARPE-19 cells retain features of native RPE cells, such as a cobblestone-like morphology and forming stable monolayers with functional polarity.
ARPE-19 cells also express RPE-specific markers like cellular retinaldehyde-binding protein (CRALBP) and RPE65, which are proteins involved in the visual cycle. They can form tight junctions, which regulate substance passage, and demonstrate transepithelial resistance, a measure of barrier function, reaching values around 50 to 100 ohms/cm² after several weeks in culture. These characteristics allow them to mimic the RPE’s role, providing a relevant model for retinal research.
Why ARPE-19 Cells Are Important for Eye Research
ARPE-19 cells are widely used in eye research because they model the retinal pigment epithelium, a cell layer involved in ocular processes. They serve as an in vitro platform for studying eye diseases, including age-related macular degeneration (AMD) and inherited retinal disorders. For instance, researchers use ARPE-19 cells to investigate cellular changes associated with AMD, such as epithelial-to-mesenchymal transition, inflammation, phagocytosis defects, and complement activation, all implicated in disease progression.
The cells are also used in testing new drugs and therapies for efficacy and toxicity before moving to animal or human trials. For example, they can assess the cytotoxic activity of ophthalmic formulations and measure their impact on specific biological markers, such as vascular endothelial growth factor (VEGF) levels, relevant in conditions like AMD. This reduces the need for animal testing in early drug development.
ARPE-19 cells help understand retinal cell biology, including RPE cell differentiation and blood-retina barrier formation. Researchers study how these cells respond to stimuli, grow, and interact, providing insights into normal RPE function and dysfunction. They can be cultured on porous filters to promote differentiation, allowing studies on their polarized secretion of proteins like pigment-epithelium-derived factor (PEDF) and VEGF, important for retinal health.
ARPE-19 cells are used in exploring gene therapy approaches for ocular conditions. Cell-based therapies, which can be pre-tested on models like ARPE-19, aim to provide broader benefits regardless of the underlying genetic cause. ARPE-19 cells provide a foundational system for studying gene expression and cellular responses relevant to such treatments.
Understanding ARPE-19 Cell Limitations
Despite their widespread use, ARPE-19 cells have limitations as a model of primary human RPE cells. As an immortalized cell line, they may exhibit abnormal karyotypes, meaning their chromosomal makeup can be altered. This immortalized nature can lead to physiological responses that differ from native RPE cells.
Over prolonged culture, ARPE-19 cells can lose some differentiated characteristics, such as their ability to metabolize vitamin A or maintain high transepithelial resistance, a measure of barrier integrity. While primary human fetal RPE cells can achieve much higher resistance values (over 200 Ωcm² and even up to 1200 Ωcm²), ARPE-19 cells typically plateau at a lower resistance, around 35 to 55 Ωcm². This indicates their barrier function may not fully replicate the in vivo environment.
Another limitation is the absence of complex interactions found in retinal tissue or an entire organism. In the eye, RPE cells interact with photoreceptors, choroidal blood vessels, and signaling molecules in a dynamic three-dimensional environment. ARPE-19 cells in a dish lack these intricate cellular and tissue-level communications, which influence their behavior. Researchers are aware of these limitations and often use ARPE-19 cells with other models, such as primary RPE cells, induced pluripotent stem cell-derived RPE cells, or animal studies, to gain a more comprehensive understanding of ocular diseases and treatments.