The Dynamic Conduct of Bone Marrow-Derived Cells in the Choroidal Neovascularization Microenvironment

Abstract

Purpose: 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 (α smooth muscle actin, α 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 α 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 α 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.