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Melissa Kaye Jones, Bin Lu, Sergey Girman, YuChun Tsai, Benjamin Bakondi, Brandon Shelley, Alexander V Ljubimov, Clive Svendsen, Shaomei Wang; In vivo study of neural progenitors after injection into a retinal degeneration rodent model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4389.
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Stem and progenitor cell transplantation provides a promising clinical application for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a single subretinal injection of human forebrain-derived neural progenitor cells (hNPCctx) into the Royal College of Surgeons (RCS) rats with inherited retinal degeneration preserved both long-term photoreceptor survival and visual function. However, grafted cells have not yet been characterized in detail. Factors promoting cell survival and migration, and the interactions between grafted and retinal cells, are still unknown. The purpose of this study was to address some of these questions.
hNPCctx were subretinally injected into RCS rats at early and middle stages of degeneration under immunosuppression. Visual function was examined by optokinetic response (OKR), electroretinography (ERG), and luminance threshold recording (LTR) from the superior colliculus. Rat retinal tissue was collected for examination of gene and protein expression.
A single subretinal injection of hNPCctx into RCS rats at early and late stages of degeneration significantly preserved both photoreceptors and visual function, as compared with sham and untreated control animals. Donor cells expressed the glial cell marker GFAP and the neural stem cell marker Nestin. Although donor cells contained pigment granules, they failed to express the typical retinal pigment epithelial cell markers RPE65 and bestrophin. Immunostaining revealed that hNPCctx secreted commponents of provisional extracellular matrix, which could possibly allow for better migration of the hNPCctx within the subretinal space.
Neural progenitors derived from fetal cortex offered dramatic preservation of vision after a single subretinal injection into a well-established rodent model of retinal degeneration. They remain as neural stem cells in vivo and have long-term survival without any evidence of unwanted pathology. Neural progenitor cells have a therapeutic potential for treating retinal degeneration.
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