Insulin-like growth factor-1 regulation of retinal progenitor cell proliferation and differentiation

Cell Cycle. 2018;17(4):515-526. doi: 10.1080/15384101.2018.1431594. Epub 2018 Apr 3.

Abstract

Strategies to improve retinal progenitor cell (RPC) capacity to yield proliferative and multipotent pools of cells that can efficiently differentiate into retinal neurons, including photoreceptors, could be vital for cell therapy in retinal degenerative diseases. In this study, we found that insulin-like growth factor-1 (IGF-1) plays a role in the regulation of proliferation and differentiation of RPCs. Our results show that IGF-1 promotes RPC proliferation via IGF-1 receptors (IGF-1Rs), stimulating increased phosphorylation in the PI3K/Akt and MAPK/Erk pathways. An inhibitor experiment revealed that IGF-1-induced RPC proliferation was inhibited when the PI3K/Akt and MAPK/Erk pathways were blocked. Furthermore, under the condition of differentiation, IGF-1-pretreated RPCs prefer to differentiate into retinal neurons, including photoreceptors, in vitro, which is crucial for visual formation and visual restoration. These results demonstrate that IGF-1 accelerates the proliferation of RPCs and IGF-1 pretreated RPCs may have shown an increased potential for retinal neuron differentiation, providing a novel strategy for regulating the proliferation and differentiation of retinal progenitors in vitro and shedding light upon the application of RPCs in retinal cell therapy.

Keywords: Retinal progenitor cell (RPC); differentiation; insulin-like growth factor-1 (IGF-1); proliferation; signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Epidermal Growth Factor / pharmacology
  • Insulin-Like Growth Factor I / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retina / cytology
  • Retinal Neurons / cytology
  • Retinal Neurons / metabolism
  • Signal Transduction / drug effects
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt

Grants and funding

This research was supported by the National Natural Science Foundations of China (81570883, 31500835), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161316), Natural Science Foundation of Ningbo Science and Technology Department (2010A610033) and The Science and Technology Commission of Shanghai (17DZ2260100)