Abstract
The aim of this study was to evaluate the effects of intravitreal injection of neural stem cells (NSCs) originating from human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on neurodegeneration of diabetic retinopathy (DR) in rats. UC-MSCs were isolated and passaged, followed by induction to NSCs in neural differentiation medium. Four weeks following NSC transplantation, treatment attenuated retinal vascular dysfunction compared with non-treated rats, and BDNF and Thy-1 expression was significantly higher in the treated group than in the control group. Treatment of diabetic rats with NSCs prevented the decrease in BDNF levels caused by diabetes. The average leakage of Evans Blue (EB) dye in the treated group was significantly less than that in the control group. These morphological improvements were accompanied by a restoration of vision, as documented by F-ERG. NSCs originating from MSCs demonstrated a neuroprotective effect by increasing the number of surviving RGCs and significantly reducing the progression of DR. Thus, transplantation of NSCs could be a novel strategy for the treatment of neurodegeneration in DR.
Highlights
Diabetic retinopathy (DR) has been considered a microcirculatory retinal disease caused by the deleterious metabolic effects of hyperglycemia[1]
We demonstrated the capacity of umbilical cord Mesenchymal stem cells (MSCs) (UC-MSCs) to differentiate into neural stem cells (NSCs) in vitro by the combination of reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence studies[8]
NSCs were differentiated from UC-MSCs, and the expression of Nestin and NeuroD1 was detected in the NSCs as previously described[8], suggesting that the molecular machinery for the neural function was activated in NSCs
Summary
Diabetic retinopathy (DR) has been considered a microcirculatory retinal disease caused by the deleterious metabolic effects of hyperglycemia[1]. Neuroretinal degeneration activates multiple signaling and metabolic pathways that participate in microangiopathy and disruption of the blood-retinal barrier (BRB), a key factor in the pathogenesis of DR. MSCs are limited to bone marrow and several types of connective tissue in adults[3]. They are capable of cloning to form adherent fibroblastic cells that express the unique properties of the cell surface phenotype. Human umbilical cord appears to be more advantageous than other stem cell sources for cell procurement, storage, and transplantation[6]. MSCs are suitable for the development of cell-based treatments for various peripheral and central nerve injuries, and MSCs may act as a potential source for neural stem cell (NSC) therapies[7].
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