Abstract
This study explored the novel strategy of hypoxic preconditioning of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) before intra vitreal transplantation to improve neuroprotective effects of Retinal Ganglion Cells (RGCs) in Acute Glaucoma Models. The methods of this research were isolated mesenchymal stem cells from the bone marrow of adult wild-type Sprague-Dawley (SD) rats. BM-MSCs were cultured under normoxic or hypoxic (1% oxygen for 24 hours) conditions. Normoxic or hypoxic BM-MSCs were transplanted intravitreally 1 week after ocular hypertension induction by acutely increasing IOP to 100 - 120 mmHg for 60 minutes. Rats were killed 4 weeks after transplanted. Apoptosis was examined by tunnel assay and expression Brn3b (Brn3b = RGCs marker) by immunohistochemical analysis of the retina. Results showed that transplantation of hypoxic preconditioning BM-MSCs in acute glaucoma models resulted in a significant apoptosis decreasing (p < 0.05) and an significant increasing in RGCs (p < 0.05), as well as enhanced mor-phologic and functional benefits of stem cell therapy versus normoxic BM-MSCs transplantation. Conclusions: Hypoxic preconditioning enhances the capacity of BM-MSCs transplantation to improve neuroprotective effects of RGCs in Acute Glaucoma Models.
Highlights
Glaucoma represents a group of diseases defined by a characteristic optic neuropathy that is consistent with excavation and undermining of the neural and connective tissue elements of the optic disc and by the eventual development of distinctive patterns of visual dysfunction [1]
Until recently it was believed that elevated intraocular pressure (IOP) plays a major role in retinal ganglion cells (RGCs) apoptosis and it is true that reduction of elevated IOP often helps in slowing down the progression of degenerative changes in glaucoma [4] [5]
The results found a significant reduction in the number of cells undergoing apoptosis with p < 0.05 in the hypoxic preconditioning (HP)-Bone Marrow Mesenchymal Stem Cells (BM-MSCs) group against control group and N-BM-MSCs group
Summary
Glaucoma represents a group of diseases defined by a characteristic optic neuropathy that is consistent with excavation and undermining of the neural and connective tissue elements of the optic disc and by the eventual development of distinctive patterns of visual dysfunction [1]. A leading cause of irreversible visual loss, is characterized by loss of retinal ganglion cells (RGCs) and their axons over a period of many years. Glaucomatous optic neuropathy is characterized by changes in the optic disc and visual field defects [2] [3]. Until recently it was believed that elevated IOP plays a major role in RGCs apoptosis and it is true that reduction of elevated IOP often helps in slowing down the progression of degenerative changes in glaucoma [4] [5]
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