title: Neuroprotective and antiapoptotic activity of lineage-negative bone marrow cells after intravitreal injection in a mouse model of acute retinal injury.
abstract: We investigated effects of bone marrow-derived, lineage-negative cell (Lin(-)BMC) transplantation in acute retinal injury. Lin(-)BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin(-)BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin(-)BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin(-)BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin(-)BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors.
authors: Department of Histology and Embryology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland ; Department of Ophthalmology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Anna
authors: A
authors: Machalińska
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Dorota
authors: 0000-0001-8884-837X
authors: D
authors: Rogińska
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Ewa
authors: E
authors: Pius-Sadowska
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Miłosz P
authors: MP
authors: Kawa
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Edyta
authors: E
authors: Paczkowska
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Michał
authors: M
authors: Rudnicki
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Renata
authors: R
authors: Lejkowska
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Bartłomiej
authors: B
authors: Baumert
authors: Department of Histology and Embryology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Barbara
authors: B
authors: Wiszniewska
authors: Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
authors: Bogusław
authors: B
authors: Machaliński