Generating retinal neurons by reprogramming retinal pigment epithelial cells

Expert Opin Biol Ther. 2010 Aug;10(8):1227-39. doi: 10.1517/14712598.2010.495218.

Abstract

Importance of the field: Retinal degenerations cause blindness. One potential therapy is cell replacement. Because the human retina lacks regeneration capacity, much attention has been directed towards searching for cells that can differentiate into retinal neurons.

Areas covered in this review: We discuss the possibility of using transcription factor genes to channel retinal pigment epithelial (RPE) cells' capabilities of proliferation and plasticity towards the production of retinal neurons.

What the reader will gain: Experiments with chick embryos show that RPE cells - in the eye, in explant, or in a dissociated cell culture - can give rise to cells resembling retinal neurons when reprogrammed with regulatory genes involved in retinal neurogenesis. Depending on the regulatory gene used, reprogramming generates cells exhibiting traits of photoreceptor cells, amacrine cells and/or young ganglion neurons.

Take home message: Gene-directed reprogramming of chick RPE can efficiently generate cells that exhibit traits of retinal neurons. Remaining to be addressed is the question of whether the results from chicks apply to mammals. Since the RPE is located adjacent to the neural retina, RPE reprogramming, if successful in mammals, may offer an approach to repopulate the neural retina without involving cell transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology*
  • Gene Expression Regulation
  • Humans
  • Nerve Regeneration* / genetics
  • Retinal Neurons / cytology
  • Retinal Neurons / metabolism
  • Retinal Neurons / physiology*
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Transcription Factors