Abstract
Purpose: :
We investigated if the transplanted bone marrow stromal cells (BMSCs) into the vitreous body of glaucoma model eye could be integrated in the host retina and also could rescue the retinal ganglion cells (RGCs) from the death induced by elevated intraocular pressure.
Methods: :
Glaucoma was induced in the right eye of adult Wister rats by ligating episcleral veins. The left eye was sham operated and used as a control. The GFP–expressing BMSCs(GFP–BMSCs) were injected into the vitreous body of both the control and the glaucomatous eyes at various glaucoma stages. Rats were sacrificed between 1week and 6 weeks after GFP–BMSCs injection, and retinas were analyzed by light microscopy. The analyses for the expression of trophic factors were performed by immunohistochemistry or real–time polymerase chain reaction (Taqman quantitative PCR). The number of RGC retrogradely labeled with Fluorogold (FG) was compared between the 4 groups (ligated episcleral veins + BMSCs, ligated episcleral veins + PBS, sham operation + BMSCs, sham operation + PBS) at 5 weeks after injection.
Results: :
One week after transplantation, GFP–BMSCs were observed to be integrated into the ganglion cell layer (GCL) and the nerve fiber layer (NFL) . At 2 or 4 weeks after transplantation, trophic factors, such as brain–derived neurotrophic factor(BDNF), ciliary neurotrophic factor(CNTF), were observed to be expressed by transplanted cells. Among the neurotrophic factors examined, bFGF and CNTF were detected to be up–regulated by Taqman quantitative PCR. The BMSCs injected glaucoma model eyes showed less reduction in the number of RGCs compared to the control glaucomatous eyes with PBS injection(gla with PBS: 1913.3±335.1/mm2 vs BMSC gla model: 2210.8±336.4/mm2 (p<0.01)).
Conclusions: :
Transplanted BMSCs could survive and express trophic factors in the glaucoma retina. In addition, the decrease in the number of RGC was less in BMSCs injected glaucoma eye. This study suggests that BMSCs transplantation may be worthy as a neuroprotective tool to treat chronic open–angle glaucoma.
Keywords: transplantation • apoptosis/cell death • intraocular pressure