Age-related macular degeneration (AMD) is characterized by the loss or 
dysfunction of retinal pigment epithelium (RPE) and is the most common cause of 
vision loss among the elderly. Stem-cell-based strategies, using human embryonic 
stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs), may provide 
an abundant donor source for generating RPE cells in cell replacement therapies. 
Despite a significant amount of research on deriving functional RPE cells from 
various stem cell sources, it is still unclear whether stem-cell-derived RPE 
cells fully mimic primary RPE cells. In this report, we demonstrate that 
functional RPE cells can be derived from multiple lines of hESCs and hiPSCs with 
varying efficiencies. Stem-cell-derived RPE cells exhibit cobblestone-like 
morphology, transcripts, proteins and phagocytic function similar to human fetal 
RPE (fRPE) cells. In addition, we performed global gene expression profiling of 
stem-cell-derived RPE cells, native and cultured fRPE cells, undifferentiated 
hESCs and fibroblasts to determine the differentiation state of 
stem-cell-derived RPE cells. Our data indicate that hESC-derived RPE cells 
closely resemble human fRPE cells, whereas hiPSC-derived RPE cells are in a 
unique differentiation state. Furthermore, we identified a set of 87 signature 
genes that are unique to human fRPE and a majority of these signature genes are 
shared by stem-cell-derived RPE cells. These results establish a panel of 
molecular markers for evaluating the fidelity of human pluripotent stem cell to 
RPE conversion. This study contributes to our understanding of the utility of 
hESC/hiPSC-derived RPE in AMD therapy.