Generation of Functional Human Retinal Ganglion Cells with Target Specificity from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental Mechanism

Stem Cells. 2017 Mar;35(3):572-585. doi: 10.1002/stem.2513. Epub 2016 Oct 26.


Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic. Stem Cells 2017;35:572-585.

Keywords: Chemically defined medium; Directed differentiation; Embryonic stem cells; Glaucoma; Induced pluripotent stem cells; Retinal ganglion cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Culture Media
  • Electrophysiological Phenomena
  • Embryonic Development* / genetics
  • Gene Expression Regulation, Developmental
  • Genes, Regulator
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Male
  • Mice
  • Repressor Proteins / metabolism
  • Retinal Ganglion Cells / cytology*
  • Retinal Ganglion Cells / metabolism
  • Signal Transduction
  • Time Factors


  • Culture Media
  • RE1-silencing transcription factor
  • Repressor Proteins