Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization.
OBJECTIVE
The pathogenesis of choroidal neovascularization (CNV) is postulated to be driven by angiogenesis, a process in which the cellular components of the new vessel complex are derived from cells resident within an adjacent preexisting capillary. Recently, an alternative paradigm, termed postnatal vasculogenesis, has been shown to contribute to some forms of neovascularization. In vasculogenesis, the cellular components of the new vessel complex are derived from circulating vascular progenitors from bone marrow. In the current study, transplantation of green fluorescent protein (GFP)-labeled bone marrow and laser-induced CNV were combined to examine the contribution of vasculogenesis to the formation of CNV.


METHODS
Ten adult C57BL/6 female mice were used as recipients for bone marrow transplantation. Bone marrow was obtained from three C57BL/6 female mice transgenic for the beta-actin promoter GFP. One month after bone marrow transplantation, CNV was induced in recipient mice by making four separate burns in the choroid of each eye with a red diode laser. Four weeks after CNV was induced, eyes of recipient mice were processed for immunohistochemistry to detect GFP and markers for vascular smooth muscle cells (alpha-smooth muscle actin, desmin, and NG2 chondroitin sulfate proteoglycan), endothelial cells (CD31, BS-1 lectin), or macrophages (F4/80).


RESULTS
GFP-labeled cells represented 17% of the total cell population in the lesion. Many of the GFP-labeled cells were immunoreactive for alpha-smooth muscle actin (39%), desmin, NG2, CD31 (41%), BS-1 lectin, or F4/80. GFP-labeled cells were morphologically indistinguishable from cells normally present in CNV lesions.


CONCLUSIONS
This study is the first to demonstrate that bone marrow-derived progenitor cells are a source of endothelial and smooth musclelike cells in CNV.
Espinosa-Heidmann
Diego G
DG
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida 33136, USA.
Caicedo
Alejandro
A
Hernandez
Eleut P
EP
Csaky
Karl G
KG
Cousins
Scott W
SW
D000199:Actins / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D015415:Biomarkers; D002829:Choroid / Q000098:blood supply / Q000601:surgery; D020256:Choroidal Neovascularization / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003893:Desmin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007202:Indicators and Reagents / Q000378:metabolism; D017075:Laser Coagulation; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000199:Actins; D000941:Antigens; D000943:Antigens, Differentiation; D015415:Biomarkers; D003893:Desmin; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C036763:monocyte-macrophage differentiation antigen