Abstract
Abstract: :
Purpose: Vasculogenesis has been postulated to contribute to some forms of pathologic neovascularization. In vasculogenesis, the cellular components of the new vessel complex are derived, in part, from bone marrow derived circulating progenitors, which differentiate into mature endothelial cells or smooth muscle cells in situ. The biological significance of vasculogenesis is unclear because no research has determined that the circulating progenitors respond differently to tissue specific angiogenic stimuli than do resident cells pre-existing within mature capillaries. We recently demonstrated that aged mice develop much more severe CNV than do young mice. We sought to determine whether bone marrow derived cells (BDMCs) contribute to choroidal neovascularization (CNV) and if BMDCs derived from old donor mice can convey increased severity into young recipients. Methods: After lethal irradiation, young (4 months) recipient mice received BDMC from aged-matched GFP-expressing donor mice. In the second experiment, young (4 months) recipient mice received bone marrow transplantation from either young or aged (18 months) donors. Laser-induced CNV was performed 1-month after reconstitution. Four weeks later, the left eyes were removed for flatmount analysis of CNV surface area, vascularity, and cellularity. The right eyes were removed and processed for imunohistochemistry. Results: Mice transplanted with GFP-BDMC showed numerous GFP positive cells within the CNV, with positive cells expressing morphology of macrophages, endothelial cells and other types. Choroidal regions adjacent to the lesion demonstrated much lower density of GFP labeled cells. Some GFP labeled cells were also present in the inner retina in regions over the CNV lesion. In the second experiment, young mice that received BDMC transplants from aged donors demonstrated more severe CNV, including increased size and vascularity compared to control mice. Conclusions: BDMCs contribute to CNV. More importantly, our preliminary data suggest that BDMC can influence the severity of CNV. Specifically, "older" BDMCs appear to transfer much of the increased severity of CNV into young recipients. BDMC may acquire age-related changes in function that increase pathological response to vascular repair.
Keywords: choroid: neovascularization • age-related macular degeneration • aging