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.

Irreversible Photoreceptors and RPE Cells Damage by Intravenous Sodium Iodate in Mice Is Related to Macrophage Accumulation

“…The results of earlier studies have suggested that the NaIO 3 injection induced macrophage accumulation in the retina, 33,44 and the macrophages phagocytose the melanin aggregations. 45 In addition, the expressions of the mRNA transcripts of Il-1b and Il-6, inflammatory cytokines induced from macrophages 46,47 increased at 3 days after the 40 mg/kg NaIO 3 injection (Fig. 8).…”

Imbalance between pro‐apoptotic and pro‐survival factors in human retinal pericytes in diabetic‐like conditions

“…Proliferating cell nuclear antigen is involved in DNA replication and repair, as it works as an auxiliary protein of DNA polymerases (Prosperi ), and its expression is positively regulated by phosphorylated MAPK (Machalińska et al. ).…”

Alteration of Neurotrophic Factors After Transplantation of Bone Marrow Derived Lin‐ve Stem Cell in NMDA‐Induced Mouse Model of Retinal Degeneration

“…NMDA injury model of mouse retina was established to study the homing of bone marrow derived Lin‐ve stem cells. Recently, the effect of bone marrow derived Lin‐ve cells was evaluated in a NaIO3‐induced retinal injury model to check their neuroprotective and antiapoptotic activity [Machalińska et al, ]. In various CNS as well as retinal disorders like glaucoma and retinal ischemia, increased glutamate levels in vitreous cavity results in oxidative stress [Dong et al, ].…”