Lgr5⁺ amacrine cells possess regenerative potential in the retina of adult mice

Aging Cell. 2015 Aug;14(4):635-43. doi: 10.1111/acel.12346. Epub 2015 May 20.

Abstract

Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5(+) amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Müller glia from Lgr5(+) amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5(+) amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases.

Keywords: Lgr5; aging; amacrine cells; neurogenesis; retina; retinal regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism*
  • Aging / genetics
  • Aging / metabolism*
  • Amacrine Cells / cytology
  • Amacrine Cells / metabolism*
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Ependymoglial Cells / cytology
  • Ependymoglial Cells / metabolism
  • Gene Expression
  • Gene Knock-In Techniques
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Neurogenesis / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Regeneration / genetics*

Substances

  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins