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

Jeffrey R. Harris, Gary A J Brown, Marda Jorgensen, Shalesh Kaushal, E. Ann Ellis, Maria B. Grant, Edward W. Scott

Research output: Contribution to journalArticle

80 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2108-2113
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

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Retinal Pigment Epithelium
Bone Marrow Cells
Wounds and Injuries
Melanosomes
Hematopoietic Stem Cells
Green Fluorescent Proteins
Bruch Membrane
Cell Fusion
Y Chromosome
Vascular Endothelial Growth Factor A
Transgenic Mice
Bone Marrow
Phenotype
Injections

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Harris, J. R., Brown, G. A. J., Jorgensen, M., Kaushal, S., Ellis, E. A., Grant, M. B., & Scott, E. W. (2006). Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury. Investigative Ophthalmology and Visual Science, 47(5), 2108-2113. https://doi.org/10.1167/iovs.05-0928

Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury. / Harris, Jeffrey R.; Brown, Gary A J; Jorgensen, Marda; Kaushal, Shalesh; Ellis, E. Ann; Grant, Maria B.; Scott, Edward W.

In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 5, 05.2006, p. 2108-2113.

Research output: Contribution to journalArticle

Harris, JR, Brown, GAJ, Jorgensen, M, Kaushal, S, Ellis, EA, Grant, MB & Scott, EW 2006, 'Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury', Investigative Ophthalmology and Visual Science, vol. 47, no. 5, pp. 2108-2113. https://doi.org/10.1167/iovs.05-0928
Harris, Jeffrey R. ; Brown, Gary A J ; Jorgensen, Marda ; Kaushal, Shalesh ; Ellis, E. Ann ; Grant, Maria B. ; Scott, Edward W. / Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury. In: Investigative Ophthalmology and Visual Science. 2006 ; Vol. 47, No. 5. pp. 2108-2113.
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AU - Grant, Maria B.

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N2 - 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.

AB - 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.

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