Abstract
Abstract: :
Purpose: CNV are comprised of two separate components: a sub–retinal capillary and an intrachoroidal component consisting of feeder vessels and vascular remodelling. Our lab and others have recently demonstrated that the sub–retinal capillary complex is partly derived from bone marrow–derived, circulating vascular progenitor cells, which form 20% of the total vascular components. In this study, we sought to determine the contribution of inflammatory cells and bone marrow–derived vascular progenitor cells to the intrachoroidal neovascular component of CNV. Methods: Chimeric GFP mice were generated by reconstituting C57/BL/6 mice with bone marrow from GFP transgenic mice. Laser induced CNV was induced one month after bone marrow transplant. Immunofluorescence staining was used to examine flatmount preparations of the choroid in areas underlying CNV away from the laser site for tissue resident monocytes, blood derived monocytes and vascular progenitor cells at day 3, 7 and 14 post CNV (n=5 per group). Results: Intrachoroidal cellular density underlying CNV increased by 95% over two weeks. During that period, the number of choroid–resident macrophages remained constant (5 cells per CNV). However, a dramatic increase in blood–derived macrophages was observed (from less than 1 to 15 cells per lesion at two weeks). The number of bone marrow–derived vascular progenitor cells in the choroid increased from 0 to 11 per lesion by day 14, representing approximately 10% of the increase density of the choroid. Conclusions: These results demonstrate that intrachoroidal vascular changes are a prominent component of this experimental model, and that bone marrow–derived progenitor cells contribute a significant component to this process. In addition, these results demonstrate that blood derived macrophages are much more numerous than resident macrophages in participating in intrachoroidal neovascularization. Intrachoroidal neovascularization is likely important biological component of neovascular macular degeneration.
Keywords: age–related macular degeneration • choroid: neovascularization • vascular cells