Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma

Exp Biol Med (Maywood). 2015 May;240(5):682-90. doi: 10.1177/1535370214560965. Epub 2015 Feb 20.

Abstract

Glaucoma is one of the leading eye diseases resulting in blindness due to the death of retinal ganglion cells. This study aimed to develop novel protocol to promote the differentiation of retinal Müller cells into ganglion cells in vivo in a rat model of glaucoma. The stem cells dedifferentiated from rat retinal Müller cells were randomized to receive transfection with empty lentivirus PGC-FU-GFP or lentivirus PGC-FU-Atoh7-GFP, or no transfection. The stem cells were induced further to differentiate. Ocular hypertension was induced using laser photocoagulation. The eyes were injected with Atoh7 expression vector lentivirus PGC-FU-Atoh7-GFP. Eyeball frozen sections, immunohistochemistry, RT-PCR, Western bolt, and apoptosis assay were performed. We found that the proportion of ganglion cells differentiated from Atoh7-tranfected stem cells was significantly higher than that of the other two groups. The mean intraocular pressure of glaucomatous eyes was elevated significantly compared with those of contralateral eyes. Some retinal Müller cells in the inner nuclear layer entered the mitotic cell cycle in rat chronic ocular hypertension glaucoma model. Atoh7 contributes to the differentiation of retinal Müller cells into retinal ganglion cells in rat model of glaucoma. In conclusion, Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma, thus opening up a new avenue for gene therapy and optic nerve regeneration in glaucoma.

Keywords: Atoh7; Glaucoma; Müller cells; retinal ganglion cells; stem cells; transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Blotting, Western
  • Cell Differentiation / physiology*
  • DNA Primers
  • Disease Models, Animal
  • Ganglia / cytology*
  • Glaucoma / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / cytology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology*

Substances

  • Atoh7 protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA Primers