Purchase this article with an account.
D.G. Espinosa–Heidmann, S. Pereira–Simon, E.P. Hernandez, Y. Piña, K.G. Csaky, S.W. Cousins; Vascular Precursor Cells From Aged Mice Transfer Age–Related Pathology Into Young Recipients . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1216. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have demonstrated that aged mice develop much more severe choroidal neovascularization (CNV) than do young mice. Recently, we have discovered that at least 25% of the cellular components of CNV, including endothelial cells (EC) or vascular smooth muscle cells (VSMC), are derived from bone marrow–derived circulating cells. Also, we have observed that bone marrow transplantation of old bone marrow into young mice transfers increased severity of CNV. Thus, we postulate that increased severity of CNV in old mice is mediated by dysfunctional EC or VSMC precursor cells derived from aging marrow. We sought to determine if the CD34 vascular precursor subpopulation was responsible for the increased severity of CNV. Methods: Purified CD34 cells derived from old C57BL/6 green fluorescent protein transgenic mice were injected intravenously into normal young wild–type mice. Laser–CNV was induced the next day. Flatmounts and immunofluorescence staining were used to compare the different groups for size and cellular infiltrate. Gene expression for various relevant markers was compared between young and old CD 34 cells by real time PCR. Results: Young mice receiving young CD34 precursors demonstrated small CNV (1.4 ± 0.4 DA) but young mice receiving aged CD34 cells developed large lesions (2.6 ± 0.7 DA, p< 0.015), the same pattern observed after whole marrow transplantation. Green–labeled transferred cells were observed to incorporate into CNV within 3 days. PCR demonstrated that old CD34 cells expressed more MMP–9 and TNF–alpha, but less beta3 integrin and VEGFR1, than did young cells. Conclusions: These data demonstrate that CD34 vascular precursors in bone marrow from old mice transfer increased CNV severity into young mice, suggesting that old precursor cells may acquire abnormalities in function that cause them to differentiate into pathological adult tissues. Preliminary data suggest altered expression of certain cytokines, growth factor receptors or cell adhesion molecules may contribute to age–related differences in function.
This PDF is available to Subscribers Only