Dendritic cells augment choroidal neovascularization.
OBJECTIVE
Dendritic cells (DCs) are innate immune cells that have recently been shown to support angiogenesis in tumors, endometriosis, and lymph nodes. A major cause of legal blindness is wet age-related macular degeneration (wet ARMD), wherein abnormal blood vessels grow under the retina, an abnormality also referred to as choroidal neovascularization (CNV). The purpose of the present study was to investigate the role of DCs in the development of CNV.


METHODS
Laser photocoagulation was used to induce CNV in C57BL/6J mice. The authors analyzed CNV lesions for the presence of DCs using flow cytometry and immunostaining at designated times. They also analyzed the effects of intravenous DC transplantation on CNV development by measuring the lesion area using confocal microscopy 1 week after laser injury.


RESULTS
The authors analyzed CNV lesions for the presence of DCs by flow cytometry and observed that CD11c(+) major histocompatibility complex (MHC) class II(+) DCs transiently infiltrated the CNV lesions, reaching a peak at 2 to 4 days after laser injury. These DCs were mostly immature (CD11c(+) MHCII(low)) and expressed vascular endothelial growth factor receptor 2. Immunostaining of laser-induced CNV lesions confirmed that DCs are located at the sites of newly formed blood vessels. Intravenously injected DCs incorporated into the CNV lesions. However, only immature DCs enhanced CNV size.


CONCLUSIONS
These results suggest a role for DCs in promoting angiogenesis and lesion growth in laser-induced CNV. The present data suggest that DCs may represent potential cellular targets for therapeutic intervention in wet ARMD.
Nakai
Kei
K
Department of Surgery, Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Fainaru
Ofer
O
Bazinet
Lauren
L
Pakneshan
Pouya
P
Benny
Ofra
O
Pravda
Elke
E
Folkman
Judah
J
D'Amato
Robert J
RJ
D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D002465:Cell Movement; D017690:Cell Transplantation; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000209:etiology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology* / Q000637:transplantation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D017075:Laser Coagulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II; D040301:Vascular Endothelial Growth Factor Receptor-2