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D. G. Espinosa-Heidmann, G. Malek, P. Saloupis, S. W. Cousins; Transplantation of Bone Marrow From Young Donors into Old Recipients Prevents Age-Related Increased Severity of Experimental CNV. Invest. Ophthalmol. Vis. Sci. 2009;50(13):778.
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We have demonstrated that aged mice develop much more severe laser-induced choroidal neovascularization (CNV) than do young mice, characterized by larger size, more fibrosis, and larger caliber vessels. Recently, we have discovered that at least 25% of the cellular components of CNV, including endothelial cells (EC) and mesenchymal cells (pericytes, myofibroblasts, smooth muscle cells) are derived from circulating bone marrow-derived progenitor cells. In preliminary data, we have observed that bone marrow transplantation of old bone marrow into young recipient mice transfers increased age-related severity of CNV. These observations suggest the hypothesis that biochemical insults acquired during aging alter marrow-derived vascular progenitors into a phenotype that induces more severe pathology. If correct, then we should be able to prevent the increased severity of aging by transplanting young marrow into aged recipients.
Laser-induced CNV was induced in young (2 months) and aged (16 months) C57BL/6 mice, or in young (n=6) or aged (n=10) mice receiving bone marrow transplants from young donors. At 2 weeks post laser, eyes were removed for flatmount analysis of CNV vascular area by lectin staining or cellular surface area by nuclear PI staining. Light microscopy for morphology and fibrosis was performed.
As expected, CNV from young mice demonstrated small surface area compared to those from old mice (1.4+0.9 disc areas compared to 3.8+1.3 disc areas, p<0.001) . Aged mice also demonstrated greater vascularity and cellularity of the CNV as well. Young mice receiving marrow from young recipient demonstrated the expected small lesions (1.6 + 0.5 DA). In contrast, aged mice receiving marrow from young mice failed to develop the expected large lesions (1.9 + 0.2 DA). The morphology of these small lesions in old mice with young marrow lacked the typical fibrosis and large caliber vessels seen in unmanipulated old mice, and the morphology was similar to the features observed in young mice.
These data demonstrate that bone marrow contains cells that regulate the size, fibrosis and vessel caliber of laser-induced CNV. We hypothesize that progenitor cells in aging marrow may acquire properties that cause them to impart pathological response to the morphology and biology of neovascularization and vessel repair.
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