Evidence for a retinal progenitor cell in the postnatal and adult mouse

Stem Cell Res. 2017 Aug:23:20-32. doi: 10.1016/j.scr.2017.06.010. Epub 2017 Jun 24.

Abstract

Progress in cell therapy for retinal disorders has been challenging. Recognized retinal progenitors are a heterogeneous population of cells that lack surface markers for the isolation of live cells for clinical implementation. In the present application, our objective was to use the stem cell factor receptor c-Kit (CD117), a surface marker, to isolate and evaluate a distinct progenitor cell population from retinas of postnatal and adult mice. Here we report that, by combining traditional methods with fate mapping, we have identified a c-Kit-positive (c-Kit+) retinal progenitor cell (RPC) that is self-renewing and clonogenic in vitro, and capable of generating many cell types in vitro and in vivo. Based on cell lineage tracing, significant subpopulations of photoreceptors in the outer nuclear layer and bipolar, horizontal, amacrine and Müller cells in the inner nuclear layer are the progeny of c-Kit+ cells in vivo. The RPC progeny contributes to retinal neurons and glial cells, which are responsible for the conversion of light into visual signals. The ability to isolate and expand in vitro live c-Kit+ RPCs makes them a future therapeutic option for retinal diseases.

Keywords: Lineage tracing; Progenitor cells; Retina; c-Kit.

Publication types

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

MeSH terms

  • Aging / physiology*
  • Animals
  • Animals, Newborn
  • Cell Lineage / drug effects
  • Cell Separation
  • Ependymoglial Cells / cytology
  • Ependymoglial Cells / drug effects
  • Ependymoglial Cells / metabolism
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Retina / cytology*
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tamoxifen / pharmacology
  • Time Factors

Substances

  • Tamoxifen
  • Green Fluorescent Proteins
  • Proto-Oncogene Proteins c-kit