Multipotential Stem Cells In The Neonatal Mammalian Eye
Adult lower vertebrates retain stem cells, show remarkable regenerative capacity and can repair damaged retina. Higher vertebrates, including adult humans, have limited stem cell capacity and cannot significantly repair damaged retina and retinal pigmented epithelial (RPE) tissues. This results in increased susceptibility to retinal injury and diseases such as age-related macular degeneration (AMD). AMD involves both degeneration of photoreceptors and RPE, and we have identified a population of multipotential stem cells in the neonatal mouse eye which we propose to test in cell transplant assays for their ability to replaced damaged RPE and photoreceptors.
Lower vertebrates including frogs, lizards and fish have remarkable regenerative capacity, including the ability to completely regenerate a damaged retina. This regenerative power is due to retention of stem cells in adult tissues. By contrast, higher vertebrates lack a significant population of stem cells in the adult eye. This lack of functional stem cells means that humans are unable to repair damage caused by age-related macular degeneration (AMD), which destroys both photoreceptor cells in the retina and the retinal pigment epithelium (RPE) which is adjacent to the retina and required for photoreceptor survival. Effective therapeutic approaches to AMD must then be directed at restoration of both photoreceptors as well as RPE. Thus, if stem cell transplants are to be used, the cells must be multipotential and able to generate both photoreceptors as well as RPE. We have isolated a novel population of multipotential stem cells from the postnatal mouse retina that can differentiate into both photoreceptors and RPE, and we propose to begin assessing the potential of these cells to replace damaged photoreceptors and RPE in mouse models. But further, these stem cells express genes required for embryonic stem cell specification, suggesting that they may retain the ability to differentiate into multiple tissues like embryonic stem cells. Indeed, we demonstrate that the cells can differentiate to produce insulin and cardiac cells. Thus in the future, this novel population of eye stem cells may represent a postnatal source of cell lineages beyond those in the eye.