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S. Wang, D. Gamm, B. Lu, N. Bischoff, S. Girman, T. Holmes, R. Shearer, C. Svendsen, R. Lund; Long Term Rescue Effect of Human Forebrain Progenitors Transplanted Into the Subretinal Space of a Rat Model of Photoreceptor Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5084.
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© ARVO (1962-2015); The Authors (2016-present)
Progressive photoreceptor degeneration is a leading and largely untreatable cause of blindness worldwide. Cell based therapies for the prevention of blindness has been shown to be effective in animal models of human disease. We have explored here the long-term rescue effect of human cortical neural progenitor cells (hNPCctx) after injection into the retina of 21 day-old RCS rats, an animal model of retinal degeneration.
Prenatal hNPCctx isolated from cortical tissue of a 94-day donor were grown as neurospheres. After >16 passages, neurospheres were dissociated into single cells, 2 x 104 cells were injected into the subretinal space of 21 day-old RCS rats that were maintained on oral cyclosporine. Functional efficacy was tested by threshold optomotor acuity and luminance thresholds recorded from the superior colliculus. All treated eyes were compared with sham-injected and untreated eyes.
Optomotor thresholds measured at P100 were significantly (p<0.001) better than shams with best results giving a figure (0.6 c/d) within normal range. Even at P150, the Optomotor acuity is still maintained over 0.5c/d, while sham and untreated animals did not track at all. Superior colliculus recordings at P100 also showed much lower luminance threshold responses in hNPCctx -treated eyes with some individual recordings within the normal range (0.3 log units). At P270, treated eyes still have significantly lower luminance threshold than sham operated controls (p<0.001). Histological studies revealed substantial photoreceptor rescue with a nearly fully preserved ONL. Donor cells formed a semi-continuous, pigmented cell layer immediately internal to host RPE and were also found scattered within the inner retina, where they remained nestin-positive and negative for retina-specific markers. Regulated cell division was observed at P150, but no sign of overgrowth.
hNPCctx are highly migratory, appear capable of adopting at least some characteristics of RPE cells and can maintain photoreceptors and visual function for a long time.
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