Abstract
Retinal pigment epithelial (RPE) cells in the back of the eye nourish photoreceptor cells and form a selective barrier that influences drug transport from the blood to the photoreceptor cells. At the molecular level, ATP-dependent efflux transporters have a major role in drug delivery in human RPE. In this study, we assessed the relative expression of several ATP-dependent efflux transporter genes (MRP1, -2, -3, -4, -5, -6, p-gp, and BCRP), the protein expression and localization of MRP1, MRP4, and MRP5, and the functionality of MRP1 efflux pumps at different maturation stages of undifferentiated human embryonic stem cells (hESC) and RPE derived from the hESC (hESC-RPE). Our findings revealed that the gene expression of ATP-dependent efflux transporters MRP1, -3, -4, -5, and p-gp fluctuated during hESC-RPE maturation from undifferentiated hESC to fusiform, epithelioid, and finally to cobblestone hESC-RPE. Epithelioid hESC-RPE had the highest expression of MRP1, -3, -4, and P-gp, whereas the most mature cobblestone hESC-RPE had the highest expression of MRP5 and MRP6. These findings indicate that a similar efflux protein profile is shared between hESC-RPE and the human RPE cell line, ARPE-19, and suggest that hESC-RPE cells are suitable in vitro RPE models for drug transport studies. Embryonic stem cell model might provide a novel tool to study retinal cell differentiation, mechanisms of RPE -derived diseases, drug testing and targeted drug therapy.
Highlights
Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of blindness in developed countries
Tyrosinase, which is important for melanin synthesis, was expressed by human embryonic stem cells (hESC)-retinal pigment epithelium (RPE) cells but not in ARPE-19 or D407 cells
There is no curative treatment for exudative AMD, human pluripotent stem cell derived RPE cells are highly desirable source of cells for cell therapy in AMD [3,4]
Summary
Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of blindness in developed countries. AMD has a multifactorial etiology and leads to a progressive loss of central vision in the elderly. AMD is characterized by the degeneration of retinal photoreceptors rod and cones, retinal pigment epithelium (RPE), and Bruch’s membrane, as well as detrimental alterations of the choroidal capillaries. One of the main functions of RPE cells is to nourish the neural cells, rod and cone cells. In senescent RPE cells, which are constantly exposed to oxidative stress, this ability is weakened, causing secondary adverse effects on the neural retina and leading to vision loss [2]. Degeneration of the postmitotic RPE cells is one of the most important hallmarks of AMD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
