Bone Marrow Cells Migrated into the Retinal Tissue of the Newborn Mice and Differentiated into Retinal Cells

Abstract

Abstract: : Purpose: We and others have recently shown that bone marrow (BM) cells can differentiate into neuronal cells in the brain. In this study, we investigated whether BM cells could have a potentiality to differentiate into retinal neuronal cells. Methods: BM cells prepared from green fluorescent protein (GFP) transgenic mice (6-8 week old) were directly injected into the heart ventricle of newborn C57/BC6 mice after whole body irradiation within 24 hours after birth. 8 week old adult mice also received GFP+BM cells through tail veins after irradiation as a control. Transplanted mice were histologically examined at 3 days and 8 weeks post BM transplantation(BMT). GFP+cells were characterized by immunostaining using antibodies against neuron specific microtubule associated protein (MAP) 2ab, astrocyte specific glial fibrillary acidic protein (GFAP) and CD45. To observe the tube-formation of endothelial cells, mice were perfused with tetramethyl rhodamine isothiocyanate (TRITC)-conjugated dextran through the left ventricle. Results: Over 90% of bone marrow cells in both newborn and adult mice became GFP positive. In newborn mice, approximately 4 % of retinal cells were GFP positive. Immunostaining revealed that some GFP+cells were expressing neuronal cell specific markers MAP and GFAP, indicating that BM cells differentiated into neuron and astrocytes. In the retina perfused with TRITC-conjugated dextran, green and red channels demonstrate the yellow tube-formation and only green channel indicate the seriously neuron or astrocyte-like cells. In contrast, BM cells did not enter the retinal cell layers of recipient adult mice. This difference may be explained by the maturity of the blood brain barrier. Our data suggest that BM cells contribute normal development of retinal tissues in the early age. Conclusion: BM contains cells capable of differentiate into retinal cells. Bone marrow transplantation may be effective to treat genetic retinal disorders such as retinitis pigmentosa if performed immediately after birth.

Keywords: regeneration • transplantation • retinal development