Purchase this article with an account.
E.J. Davies, B.J. Chen, D. DeOliveira, G. Homayounfar, N.J. Chao, D.W. Rickman; Cells From Transplanted Adult Bone Marrow and Fetal Blood Contribute to Homeostatic Remodeling of the Ocular Perivascular Microenvironment . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1775.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the fates of hematopoietically–derived cells in the homeostatic maintenance of the non–injured ocular vascular microenvironment and to lay the foundation for their use in vascular repair in the treatment of retinal hypoxic injury.
C57BL/6 mice were lethally irradiated and transplanted, via tail vein injection, with 1 X 107 GFP–labeled cells from T–cell–depleted adult bone marrow (BM) or 1 X 106 cells from full–term fetal blood (FB, a experimental model of umbilical cord blood). Mice were sacrificed at 1–6 mo following transplantation, and eyes were dissected, cryosectioned and processed for fluorescence microscopy using the nuclear stain, DAPI, and antibodies to retinal cell type–specific markers [rhodopsin, recoverin, protein kinase C (α–PKC) and glial fibrilary acidic protein (GFAP)] or endothelial– (CD31), macrophage– (F4/80) and panleukocyte– (CD45) specific antigens. All secondary antibodies were conjugated to Cy3.
All animals displayed hematopoietic reconstitution (>95% full chimerism) at 1 mo. Analysis of DAPI–stained retinal sections showed no evidence of non–specific radiation–induced thinning of nuclear layers at any time point examined. Furthermore, staining with retinal cell type–specific markers showed normal distributions of photoreceptor and bipolar cells, as well as a lack of Müller cell hypertrophy. In both BM– and FB–transplanted animals, GFP+ cells were closely associated with the retinal, ciliary, choroidal and scleral vasculature at all time points. Most cells were confined to the lumina of vessels, and many were CD45+. Within choroidal vessels, in particular, numerous elongated GFP+ cells were seen in close apposition to the luminal surface, but no conclusive GFP+/CD31+ cells were observed. GFP+ cells were also abluminal to CD31+ endothelial cells and often contained CD31+ intracytoplasmic inclusions, indicating active endothelial cell phagocytosis. In addition, many perivascular GFP+ cells were F4/80+, further confirming their roles as macrophages.
Transplanted cells from BM or FB can contribute to the homeostatic, phagocytic remodeling of the ocular vasculature. Although we observed no evidence of a GFP+ cell contribution to the vascular endothelium in this non–injury model, determination of the full potential of transplantation in vascular repair awaits testing in a model of hypoxic injury. Nevertheless, here we demonstrate the potential utility of both BM and umbilical cord blood in this process.
This PDF is available to Subscribers Only