Müller Cells Derived from Adult Chicken and Mouse Retina Neurospheres Acquire the Dopaminergic Phenotype

Cell Mol Neurobiol. 2019 Jan;39(1):99-109. doi: 10.1007/s10571-018-0636-z. Epub 2018 Nov 14.

Abstract

Neurospheres prepared from multipotent progenitors in the retina obtained from postnatal mice differentiate into neurons and Müller glia (De Melo Reis et al., in Cell Mol Neurobiol 31:835-846, 2011). Here, we investigated whether neurospheres prepared from adult chickens (ciliary marginal zone, CMZ) or (ciliary body) retina could also lead to differentiated neurons and glia. Neurospheres were prepared from post-hatched chickens or from adult mice after 7 days in the presence of mitogenic factors (FGFb, insulin, and EGF), generating neurons and glial cells. In addition, Müller (2M6 or glutamine synthetase positive cells) derived from post-hatch chicken CMZ neurospheres displayed the dopaminergic phenotype. Furthermore, we observed that Müller cells derived from adult chickens and mice retina neurospheres released significant amounts of dopamine as well as of its metabolites. Taken together, our data lead us to conclude that as for embryonic (chick) or newborn (mouse), the dopaminergic phenotype is a default condition of Müller glial cells obtained from neurospheres prepared from mature retina. Our data raise the possibility that Müller cells from differentiated tissue could be used to ameliorate neurodegenerative diseases involving dopaminergic dysfunction as in Parkinson's disease as shown previously (Stutz et al., in J Neurochem 128:829-840, 2014).

Keywords: Dopamine; Müller glial cells; Neurospheres; Retina; Retinal ganglion cells; Tyrosine hydroxylase.

MeSH terms

  • Aging / metabolism*
  • Animals
  • Animals, Newborn
  • Cell Separation
  • Cells, Cultured
  • Chickens
  • Dopamine / metabolism*
  • Ependymoglial Cells / cytology*
  • Ependymoglial Cells / metabolism
  • Metabolome
  • Mice, Inbred C57BL
  • Phenotype
  • Retina / cytology*
  • Spheroids, Cellular / cytology*
  • Spheroids, Cellular / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Tyrosine 3-Monooxygenase
  • Dopamine