Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina. Academic Article uri icon

Overview

abstract

  • To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.

publication date

  • March 3, 2016

Research

keywords

  • Cell Movement
  • Eye Proteins
  • Models, Biological
  • Photoreceptor Cells, Vertebrate
  • Retinal Diseases
  • Signal Transduction

Identity

PubMed Central ID

  • PMC4776098

Scopus Document Identifier

  • 84960156616

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0068422

PubMed ID

  • 26935401

Additional Document Info

volume

  • 6