Neuroprotection of Transplanting Human Umbilical Cord Mesenchymal Stem Cells in a Microbead Induced Ocular Hypertension Rat Model

Abstract

ABSTRACTPurpose: The purpose of this study is to investigate the potential therapeutic benefits of intravitreally transplanted human umbilical cord mesenchymal stem cells (UC-MSCs) in an animal model of microbead-injection-induced ocular hypertension (OHT).Methods: UC-MSCs were isolated from human umbilical cords and then cultured. The OHT model was induced via intracameral injection of polystyrene microbeads in Sprague–Dawley adult rat eyes. Fifty-four healthy adult rats were randomly divided into three groups: normal control, OHT model treated with intravitreal transplantation of UC-MSCs, or phosphate-buffered saline (PBS). Two days after OHT was induced, either 5 µl 105 UC-MSCs suspension or PBS was injected into the vitreous cavity of rats. UC-MSCs localization and integration were examined via immunohistochemistry. Neuroprotection was quantified by counting retinal ganglion cells (RGCs) and axons 2 weeks following transplantation. The expression levels of glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) were assessed via immunohistochemistry and Western blot. Functional recovery was assessed 2 weeks after transplantation via scotopic threshold response (STR) electroretinography.Results: Elevated IOP levels were sustained at least 3 weeks after intracameral microbead injection and the number of β-III-tubulin+ RGCs significantly declined compared to PBS-injected eyes. UC-MSCs survived for at least 2 weeks after intravitreal transplantation and predominantly located in the vitreous cavity. A fraction of cells migrated into the ganglion cell layer of host retina, but without differentiation. Intravitreal UC-MSC transplantation resulted in increased number of RGCs, axons, and increased expression of GDNF and BDNF but decreased expression of GFAP. Intravitreal delivery of UC-MSCs significantly improved the recovery of the positive STR.Conclusions: Intravitreal transplantation of UC-MSCs revealed the neuroprotection in the microbead-injection induced OHT. The effects could be related to the secretion of tropic factors (BDNF and GDNF) and the modulation of glial cell activation.