Bone marrow-derived cells home to and regenerate retinal pigment epithelium after injury.
OBJECTIVE
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.
Harris
Jeffrey R
JR
Program in Stem Cell Biology, University of Florida, Gainesville, Florida 32610, USA.
Brown
Gary A J
GA
Jorgensen
Marda
M
Kaushal
Shalesh
S
Ellis
E Ann
EA
Grant
Maria B
MB
Scott
Edward W
EW
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016570:Bruch Membrane / Q000187:drug effects / Q000293:injuries; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D020256:Choroidal Neovascularization / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017404:In Situ Hybridization, Fluorescence; D007452:Iodates / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D007452:Iodates; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D049452:Green Fluorescent Proteins; C032285:sodium iodate