The dynamic conduct of bone marrow-derived cells in the choroidal neovascularization microenvironment.
OBJECTIVE
Choroidal neovascularization (CNV) is one of the most frequent causes of severe and progressive vision loss. Prior studies have shown that bone marrow-derived cells (BMCs) play an important role in CNV, indicating that BMCs can be a potential target for inhibiting the development of CNV. It could be helpful for our understanding of CNV to study the dynamic conduct of BMCs in the CNV microenvironment.


METHODS
Green fluorescent protein (gfp) chimeric mice were developed by transplanting bone marrow cells from gfp+/+ transgenic mice to adult C57BL/6J mice. The chimeric mice underwent laser rupture of Bruch's membrane to induce CNV and were killed at 1, 2, 3, and 4 weeks after laser injury. The eyes were enucleated and processed for immunofluorescence to detect markers for vascular smooth muscle cells (alpha smooth muscle actin, alpha SMA), endothelial cells (CD31), or macrophages (F4/80) on gfp+ cells. All sections were qualitatively and quantitatively assessed by confocal microscopy.


RESULTS
Large number of gfp-labeled cells appeared in the lesions and integrated into CNV. Gfp+ cells, which were immunoreactive for alpha SMA, CD31, or F4/80, can be detected through the whole study. The constituent ratio of those three cell-types in total gfp+ cells in CNV altered as CNV developed. The maximal ratios of CD31-labeled cells and F4/80-labeled cells presented at 2 week, while the ratio of alpha SMA-labeled cells upgraded continuously.


CONCLUSIONS
BMCs underwent a serial of changes in position and expression during the progression of CNV. Those changes may result from the interaction between BMCs and the CNV microenvironment.
Hou
Hui-Yuan
HY
Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Wang
Yu-Sheng
YS
Xu
Jian-Feng
JF
Wang
Yao-Chun
YC
Liu
Jin-Ping
JP
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D020256:Choroidal Neovascularization / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*
D000199:Actins; D000943:Antigens, Differentiation; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C036763:monocyte-macrophage differentiation antigen; D049452:Green Fluorescent Proteins