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Bin Lu, SiokLam Lim, WenLin Li, Catherine W. Morgans, sergje girman, Justine Smith, Ray Lund, Sheng Ding, Kang Zhang, Shaomei Wang; Human Embryonic Derived Neural Stem Cells Preserved Vision in Rodent Retinal Degeneration Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3176.
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Cell-based therapies have shown promise as a rescue strategy for the clinical treatment of degenerative diseases. Until somatic cell nuclear transfer or induced pluripotent stem cell technology is further developed, human embryonic stem cells (hESC) have been considered a reliable source of specific cell types for cell-based therapy. The purpose of this study is to investigate whether hESC-derived neural stem cells (NSCs) can preserve vision when injected into the Royal College of Surgeons (RCS) rat -a retinal degeneration model.
hESC-NSCs were generated by differentiation of hESC into NSCs with small molecules and chemically defined media. RCS rats received subretinal injections of NSCs (n=14) at postnatal (P) day 21; medium-injected (n=10) and untreated (n=10) animals were used as controls. Optokinetic responses and luminance thresholds were measured to test visual function at P60-150. Retinal immunohistochemistry was performed at the end of experiment.
hESC-NSC-treated eyes showed significantly better visual acuity than controls (0.52c/d versus 0.28c/d, p<0.001) at P90. Luminance threshold recordings from the superior colliculus detected much lower luminance thresholds in cell treated eyes compared with controls (0.4log units vs. 3.1log units P< 0.001). Correlated with functional preservation, substantial photoreceptor preservation (8 layers vs. a single layer) was observed in cell- treated retinas compared with controls. hESC-NSCs, identified with a human-specific antibody, were distributed in the subretinal space as a continuous layer, and were also identified within the inner retina. The injected hESC-NSCs were not found to express retinal cell markers; however, additional immunostaining correlated photoreceptor preservation with increased CD11b and FGF2 expression in the cell-injected eyes.
hESC-NSCs can preserve vision after subretinal injection. The mechanism of hESC-NSC in protecting photoreceptors and visual function is partly through modifying retinal microglia responses, rather than differentiating into/replacing retinal neurons.
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