Abstract
Glaucoma is the leading cause of irreversible blindness worldwide, and pathologically elevated intraocular pressure (IOP) is the major risk factor. Neuroprotection is one of the potential therapies for glaucomatous retinal damage. Intravitreal mesenchymal stem cell (MSC) transplantation provides a viable therapeutic option, and human umbilical cord- (hUC-) MSCs are attractive candidates for cell-based neuroprotection. Here, we investigated the ability of transplanted hUC-MSCs to survive and migrate within the vitreous cavity and their neuroprotective effects on chronic glaucomatous retina. For this, we developed a chronic ocular hypertension (COH) rat model through the intracameral injection of allogeneic Tenon's fibroblasts. Green fluorescent protein-transduced hUC-MSCs were then injected into the vitreous cavity one week after COH induction. Results showed that a moderate IOP elevation lasted for two months. Transplanted hUC-MSCs migrated toward the area of damaged retina, but did not penetrate into the retina. The hUC-MSCs survived for at least eight weeks in the vitreous cavity. Moreover, the hUC-MSCs were efficient at decreasing the loss of retinal ganglion cells; retinal damage was attenuated through the inhibition of apoptosis. In this study, we have developed a novel COH rat model and demonstrated the prolonged neuroprotective potential of intravitreal hUC-MSCs in chronic glaucoma.
Highlights
Glaucoma comprises a group of diseases causing irreversible blindness characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons
In the chronic ocular hypertension (COH)+HUC-mesenchymal stem cell (MSC) group, retinal damage in the ganglion cell layer (GCL) was reduced, and the number of RGC was higher than that in the COH group. These results suggest that human umbilical cord- (hUC-)MSCs had protective effects on RGCs and against GCL injury, but had no effects on inner plexiform layer (IPL) and outer nuclear layer (ONL) injury caused by high intraocular pressure (IOP)
In combination with subsequent findings regarding the loss of retinal RGCs, the thinning of the retina, and the appearance of retinal cell apoptosis caused by elevated IOP, our results suggest that the experimental rat model meets the requirement for a chronic glaucoma model
Summary
Glaucoma comprises a group of diseases causing irreversible blindness characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. The common pharmacological or surgical treatments to reduce IOP do not halt progressive visual loss [1]; besides lowering IOP, alternative treatment approaches for glaucoma are needed. Current studies of cell-based neuroprotective therapies in animal models have introduced a new possibility for amelioration of retinal degeneration [2, 3]. Mesenchymal stem cells (MSCs) of different origins have shown the greatest potential in the treatment of optical neuropathy [4,5,6]. Intravitreal transplantation of human umbilical cord (hUC) blood stem cells or dental pulp stem cells is neuroprotective for RGCs in rats with optic injury [6,7,8,9]. An emerging alternative is the use of hUC-MSCs, which are derived from Wharton’s jelly, the particular connective
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