4.3 Review

Generating retinal neurons by reprogramming retinal pigment epithelial cells

Journal

EXPERT OPINION ON BIOLOGICAL THERAPY
Volume 10, Issue 8, Pages 1227-1239

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1517/14712598.2010.495218

Keywords

cell-replacement; photoreceptors; regeneration; retinal ganglion cells; transcription factors

Funding

  1. National Institutes of Health/National Eye Institute (NIH/NEI) [R01 EY011640]
  2. EyeSight Foundation of Alabama
  3. Research to Prevent Blindness (to the Department of Opthalmology, University of Alabama at Birmingham)

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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.

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