Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13654-9. doi: 10.1073/pnas.0402129101. Epub 2004 Sep 7.


It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Eye Proteins
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • Male
  • N-Methylaspartate / toxicity*
  • Nerve Regeneration*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / cytology
  • Neurons / drug effects*
  • Neurons / pathology
  • Neurons / physiology*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / pathology*
  • Rhodopsin / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Tretinoin / pharmacology


  • Basic Helix-Loop-Helix Transcription Factors
  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, rat
  • Repressor Proteins
  • Trans-Activators
  • cone rod homeobox protein
  • Neurogenic differentiation factor 1
  • Tretinoin
  • N-Methylaspartate
  • Rhodopsin