Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist

Neuroscience. 2017 Mar 27;346:437-446. doi: 10.1016/j.neuroscience.2017.01.029. Epub 2017 Jan 29.

Abstract

Irreversible vision loss due to disease or age is responsible for a reduced quality of life. The experiments in this study test the hypothesis that the α7 nicotinic acetylcholine receptor agonist, PNU-282987, leads to the generation of retinal neurons in an adult mammalian retina in the absence of retinal injury or exogenous growth factors. Using antibodies against BrdU, retinal ganglion cells, progenitor cells and Müller glia, the results of this study demonstrate that multiple types of retinal cells and neurons are generated after eye drop application of PNU-282987 in adult Long Evans rats in a dose-dependent manner. The results of this study provide evidence that progenitor cells, derived from Müller glia after treatment with PNU-282987, differentiate and migrate to the photoreceptor and retinal ganglion cell layers. If retinas were treated with the alpha7 nAChR antagonist, methyllycaconitine, before agonist treatment, BrdU-positive cells were significantly reduced. As adult mammalian neurons do not typically regenerate or proliferate, these results have implications for reversing vision loss due to neurodegenerative disease or the aging process to improve the quality of life for millions of patients.

Keywords: BrdU; Long Evans rats; Müller glia; alpha7 nAChRs; retina; retinal ganglion cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Benzamides / administration & dosage*
  • Bridged Bicyclo Compounds / administration & dosage*
  • Bromodeoxyuridine
  • Cell Movement / drug effects
  • Ependymoglial Cells / drug effects
  • Ependymoglial Cells / physiology
  • Female
  • Male
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / physiology
  • Rats
  • Rats, Long-Evans
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / physiology
  • Retinal Neurons / drug effects*
  • Retinal Neurons / physiology*
  • alpha7 Nicotinic Acetylcholine Receptor / agonists*

Substances

  • Benzamides
  • Bridged Bicyclo Compounds
  • PNU-282987
  • alpha7 Nicotinic Acetylcholine Receptor
  • Bromodeoxyuridine