Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury

Invest Ophthalmol Vis Sci. 2006 May;47(5):2108-13. doi: 10.1167/iovs.05-0928.

Abstract

Purpose: To determine whether hematopoietic stem and progenitor cells (HSCs/HPCs) can home to and regenerate the retinal pigment epithelium (RPE) after induced injury.

Methods: Enriched HSCs/HPCs from green fluorescent protein (gfp) transgenic mice were transplanted into irradiated recipient mice to track bone marrow-derived cells. Physical damage was induced by breaching Bruch's membrane and inducing vascular endothelial growth factor A (VEGFa) expression to promote neovascularization. RPE damage was also induced by sodium iodate injection (40 mg/kg) into wild-type or albino C57Bl/6 mice. Cell morphology, gfp expression, the presence of the Y chromosome, and the presence of melanosomes were used to determine whether the injured RPE was being repaired by the donor bone marrow.

Results: Injury to the RPE recruits HSC/HPC-derived cells to incorporate into the RPE layer and differentiate into an RPE phenotype. A portion of the HSCs/HPCs adopt RPE morphology, express melanosomes, and integrate into the RPE without cell fusion.

Conclusions: HSCs/HPCs can migrate to the RPE layer after physical or chemical injury and regenerate a portion of the damaged cell layer.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Bruch Membrane / drug effects
  • Bruch Membrane / injuries
  • Cell Differentiation / physiology
  • Cell Movement / physiology*
  • Choroidal Neovascularization / metabolism
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Green Fluorescent Proteins / genetics
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • In Situ Hybridization, Fluorescence
  • Iodates / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pigment Epithelium of Eye / drug effects
  • Pigment Epithelium of Eye / physiology*
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / physiology*

Substances

  • Iodates
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Green Fluorescent Proteins
  • sodium iodate