The retinal pigmented epithelium - from basic developmental biology research to translational approaches

The development of the eye has been a topic of extensive investigation, from the early studies on tissue induction to more recent breakthroughs in resolving the mechanism regulating progenitor patterning and their gradual and coordinated differentiation into diverse tissue types that function together throughout life. Among the ocular tissue types, the retinal pigmented epithelium (RPE) is at the forefront of developmental biology and stem cell research. The growing interest in this lineage stems from its importance for photoreceptor function as well as from its requirement during embryogenesis for the development of the photoreceptors and the choroid. Indeed mutations in RPE genes and epigenetic changes that occur during aging are the cause of monogenic as well as multifactorial retinal diseases. Importantly, the RPE is readily generated from stem cells, and these stem cell-derived RPE cells are currently being tested in clinical trials for transplantation in cases of retinal dystrophies; they also constitute an important model to study developmental processes in vitro. This review summarizes recent advances in our understanding of RPE development and its requirement for the development of photoreceptors and choroidal vasculature. We discuss the contribution of basic findings to therapeutic applications and the future challenges in uncovering developmental processes and mimicking them ex vivo to further advance research and therapy of retinal disorders.