Maximizing functional photoreceptor differentiation from adult human retinal stem cells

Stem Cells. 2010 Mar 31;28(3):489-500. doi: 10.1002/stem.279.


Retinal stem cells (RSCs) are present in the ciliary margin of the adult human eye and can give rise to all retinal cell types. Here we show that modulation of retinal transcription factor gene expression in human RSCs greatly enriches photoreceptor progeny, and that strong enrichment was obtained with the combined transduction of OTX2 and CRX together with the modulation of CHX10. When these genetically modified human RSC progeny are transplanted into mouse eyes, their retinal integration and differentiation is superior to unmodified RSC progeny. Moreover, electrophysiologic and behavioral tests show that these transplanted cells promote functional recovery in transducin mutant mice. This study suggests that gene modulation in human RSCs may provide a source of photoreceptor cells for the treatment of photoreceptor disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cells, Cultured
  • Gene Expression Regulation / genetics
  • Graft Survival / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Mice
  • Otx Transcription Factors / genetics
  • Photoreceptor Cells, Vertebrate / cytology*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Retina / cytology*
  • Retina / metabolism
  • Stem Cell Transplantation / methods*
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Trans-Activators / genetics
  • Transcription Factors / genetics
  • Transducin / genetics
  • Transduction, Genetic / methods
  • Transfection / methods
  • Transplantation, Heterologous / methods*


  • Homeodomain Proteins
  • Otx Transcription Factors
  • Otx2 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Vsx2 protein, mouse
  • cone rod homeobox protein
  • Transducin