Abstract
Retinal degeneration is a prominent feature in ocular disorders. In exploring possible treatments, Mesenchymal Stem Cells (MSCs) have been recognized to yield therapeutic role for retinal degenerative diseases. Studies have also displayed that erythropoietin (EPO) administration into degenerative retina models confers significant neuroprotective actions in limiting pathological cell death. In this study, we aimed to use MSCs to deliver EPO and to evaluate the ability of EPO to rescue retinal neurons from dying upon reactive oxidative stress induction. We derived human MSCs from Wharton’s jelly (hWJMSCs) of the umbilical cord and cells were transduced with lentivirus particles encoding EPO and a reporter gene of green fluorescent protein (GFP). The supernatants of both transduced and non-transduced cells were collected and used as a pre-conditioning medium for Y79 retinoblastoma cells (retinal neuron cell line) following exposure to glutamate induction. Retinal cells exposed to glutamate showed reduced mitochondrial depolarization and enhanced improvement in cell viability when incubated with pre-conditioned media of transduced cells. Our results established a proof-of-concept that MSCs could be used as a candidate for the delivery of EPO therapeutic gene in the treatment of retinal degenerations.
Highlights
Retinal degeneration is a structural defect acquired in both inherited (Shintani et al, 2009; Daiger et al, 2013; Tomita et al, 2013) and sporadic ocular disorders (Punzo et al, 2012; Sobrin and Seddon, 2014), such as Age-related Macular Degeneration (AMD) and retinitis pigmentosa
Post-transplanted Mesenchymal Stem Cells (MSCs) was evidenced to transdifferentiate into retinal neurons (Tomita et al, 2002; Kicic et al, 2003; Arnhold et al, 2006; Castanheira et al, 2008; Tao et al, 2010; González-Garza and MorenoCuevas, 2012; Guan et al, 2013; Hu et al, 2013) and retinal pigment epithelium (Vossmerbaeumer et al, 2009; Huang et al, 2012; Guan et al, 2013) in both in vitro and in vivo studies
Bhd. (Cyberjaya, Malaysia). hWJMSCs were expanded at a density of 3000 cells/cm2 in a 25-cm2 plastic flask containing 5 mL of MSC culture media composing of Dulbecco’s Modified Eagle Medium with nutrient mixture F-12 (DMEM/F12) medium (Gibco; USA) supplemented with 10% Fetal Bovine Serum (FBS; Gibco), 100 units/mL of penicillin (Gibco), and 100 μg/mL of streptomycin (Gibco)
Summary
Retinal degeneration is a structural defect acquired in both inherited (Shintani et al, 2009; Daiger et al, 2013; Tomita et al, 2013) and sporadic ocular disorders (Punzo et al, 2012; Sobrin and Seddon, 2014), such as Age-related Macular Degeneration (AMD) and retinitis pigmentosa. Post-transplanted MSCs was evidenced to transdifferentiate into retinal neurons (Tomita et al, 2002; Kicic et al, 2003; Arnhold et al, 2006; Castanheira et al, 2008; Tao et al, 2010; González-Garza and MorenoCuevas, 2012; Guan et al, 2013; Hu et al, 2013) and retinal pigment epithelium (Vossmerbaeumer et al, 2009; Huang et al, 2012; Guan et al, 2013) in both in vitro and in vivo studies
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