Induced Pluripotent Stem Cells Generate Both Retinal Ganglion Cells and Photoreceptors: Therapeutic Implications in Degenerative Changes in Glaucoma and Age-Related Macular Degeneration

Abstract

Abstract The direct reprogramming of somatic cells to a pluripotent state holds significant implications for treating intractable degenerative diseases by ex vivo cell therapy. In addition, the reprogrammed cells can serve as a model for diseases and the discovery of drugs and genes. Here, we demonstrate that mouse fibroblast induced pluripotent stem cells (iPSCs) represent a renewable and robust source of retinal progenitors, capable of generating a wide range of retinal cell types that includes retinal ganglion cells (RGCs), cone, and rod photoreceptors. They respond to simulated microenvironment of early and late retinal histogenesis by differentiating into stage-specific retinal cell types through the recruitment of normal mechanisms. The depth of the retinal potential of iPSCs suggests that they may be used to formulate stem cell approaches to understand and treat a wide range of retinal degenerative diseases from glaucoma to age-related macular degeneration (AMD).