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N. Goldenberg-Cohen, B. R. Avraham, D. Weinberger; Enhanced Neuronal Differentiation of Bone Marrow Derived Stem Cells in Ischemic Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4095.
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To enhance neuronal differentiation of adult bone marrow-derived stem cell (BMSCs) in the retina, following induction of ischemic optic neuropathy.
C57Bl6 mice underwent syngeneic transplantation of whole bone marrow cells (wBMC) from GFP donors to generate full chimeras. After three months, the mice bone marrow was mobilized with GM-CSF (5 daily doses of 15 µg/g) and one of the eyes was injured. Ischemic optic neuropathy (AION) was induced by laser photosensitization of intravenously-injected Rose Bengal over the optic disc. The contralateral eyes served as negative controls. The next day the mice were injected (intravitreously) with 5 µg of brain derived neurotrophic factor (BDNF). After 4 weeks the eyes were enucleated and analyzed by immunohistochemistry for expression of differentiation markers in the GFP-positive bone marrow cells.
in BDNF-treated eyes, the GFP labeled BMSC homed to and incorporated in the ischemic retina, in particular in the retinal ganglion (RGC) and inner plexiform layers. The GFP-labeled cells in the RGC layer were positive for neuronal markers. Glial, endothelial and myeloid differentiation were observed in other layers of the retina.
In previous studies we showed that bone marrow-derived stem and progenitor cells homed to the injured layers retina efficiently and selectively. In this study, the response of these cells to local injury signals was promoted by exogenous administration of BDNF. We found a marked increase in number of cells expressing neuronal markers in the RGC layer, development of dendritic extensions to the adjacent cells within 4 weeks after the insult. These data serve the basis for further assessment of the functional involvement of bone marrow-derived cells to retinal injury.
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