The role of adult bone marrow-derived stem cells in choroidal neovascularization.
OBJECTIVE
Age-related macular degeneration (ARMD) is the primary cause of blindness in people aged of 50 years or more. The wet form leads to severe loss of central vision. Recent evidence supports that adult hematopoietic stem cells (HSCs) contribute to preretinal neovascularization. In the current study, it was determined whether HSCs, by producing both blood and blood vessels, provide functional hemangioblast activity during choroidal neovascularization (CNV) in mice.


METHODS
Gfp chimeric mice were developed by bone marrow ablation of C57BL/6J mice and reconstitution with donor tissue from gfp(+/+) transgenic mice. Gfp chimeric mice underwent laser rupture of Bruch's membrane and were killed and eyes enucleated at 1, 2, 3, and 4 weeks after laser injury. CNV was examined by confocal microscopy of retinal flatmounts. Because endothelial progenitor cells (EPCs) derive from HSCs, immunocytochemistry was used to quantify relative the EPC contribution to CNV.


RESULTS
Laser injury alone was sufficient to induce stem cell recruitment and subsequent CNV. Gfp+ cells formed part of the functional vasculature in the choroid as early as 1 week after injury and were present for the duration of the study. The relative EPC contribution to CNV remained fairly constant throughout the study and constituted almost 50% of the total vasculature.


CONCLUSIONS
Adult stem cells are recruited to the choroid in a model of CNV, where they contribute to forming aberrant new vessels. This observation suggests that targeting stem cell recruitment to the eye may offer a novel therapeutic strategy for ARMD.
Program in Stem Cell Biology, University of Florida, Florida, USA.
Nilanjana
N
Sengupta
Sergio
S
Caballero
Robert N
RN
Mames
Jason M
JM
Butler
Edward W
EW
Scott
Maria B
MB
Grant
D000818:Animals; D001773:Blood Cells / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D001853:Bone Marrow / Q000528:radiation effects; D016570:Bruch Membrane / Q000601:surgery; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000503:physiopathology*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D007202:Indicators and Reagents / Q000378:metabolism; D017075:Laser Coagulation; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins