Elucidating the Mechanisms of Developmental Cell Death in the Retina Using Stem Cell-derived Organoids

The development of stem cell technologies has opened up new opportunities for research and therapeutic development that, until recently, were unavailable. In particular, the development of human stem cell derived 3D tissues or “organoids” that recapitulate the native histoarchitecture, and to some degree the native functionality, have provided incredible advancements in our understanding of human physiology and disease. In this study we take advantage of retinal organoids as a new model to study the mechanisms of cell death affecting retinal ganglion cells during human development. Human induced pluripotent stem cells (hiPSC) were directed to follow a neuronal lineage and were then further differentiated into 3D retinal tissue. Retinal organoids were collected at various time points during development and analyzed using Western blot and immunofluorescent staining for retinal ganglion cells and programmed cell death markers. Our results show the role of programmed cell death as a mechanism to control retinal ganglion cell numbers during development. This has important consequences for understanding not only basic developmental processes, but also the basis of congenital retinal abnormalities that can lead to diseases of vision. Moreover, this knowledge has potential impact for translational research using retinal organoid models. Support or Funding Information This work was supported, in part, by a Challenge Grant to the Department of Ophthalmology at the University of Colorado from Research to Prevent Blindness.