Effects of bone marrow mesenchymal stem cells transfected with Ang-1 gene on hyperoxia-induced optic nerve injury in neonatal mice.

ABSTRACT

Optic nerve injury triggered retinal ganglion cell (RGC) death and optic nerve atrophy lead to visual loss. Bone marrow mesenchymal stem cells (BMSCs) are stromal cells, capable of proliferating and differentiating into different types of tissues. This aims of this study is to investigate the role of BMSCs transfected with angiopoietin-1 (Ang-1) in optic nerve injury induced by hyperoxia in a neonatal mice model. Ang-1 overexpression vector was constructed and used to transfect BMSCs. Reverse transcription-quantitative polymerase chain reaction was performed to detect Ang-1 expression in BMSCs. The hyperoxia-induced optic nerve injury model was established. The optic nerves at 6-7 mm posterior to the eyeball were extracted, and were treated with luxol fast blue staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy to examine the effects of Ang-1-modified BMSCs on optic nerve injury induced by hyperoxia. The mice in the Ang-1 + BMSCs and BMSCs groups showed remarkably improved myelin sheaths of nerve fibers compared to the hyperoxia saline group. The positive expression and integrated optic density of Ang-1 in the Ang-1 + BMSCs group were significantly higher compared to the air control, hyperoxia saline and BMSCs groups. The number and diameter of myelinated nerve fibers, the diameter of axons and the thickness of myelin sheath in the air control and Ang-1 + BMSCs groups were higher compared to the hyperoxia saline group. Our study provides evidence supporting that Ang-1-modified BMSCs may have preventive and therapeutic effects on hyperoxia-induced optic nerve injury in neonatal mice.