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Bin Lu, YuChun Tsai, Grazyna Adamus, Sergey Girman, Lin Shen, David Gamm, Catherine Morgans, Brandon Shelley, Clive Svendsen, Shaomei Wang; Effect of Repeated Delivery of Neural Progenitors on Vision Preservation in RCS Rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4112.
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Growth factor mediated neuroprotection has been repeatedly demonstrated in multiple animal models and current clinical trial using CNTF to treat retinal degeneration. Stem/progenitor cells as factor delivery vehicle offer great promise to slow down the progression of degenerative diseases. To sustain protective effect for long term, repeated grafting of stem cells is necessary. However, some fundamental questions are remained to be addressed, such as how will host response to the second injection, how the efficacy of the first graft will be affected etc. Here we proposed to address these questions by repeated delivery of human neural progenitor cells into the Royal College Surgeon (RCS) rats.
Human neural progenitor cells (hNPC) produced under GLP condition were unilaterally injected into the subretinal space of RCS rats at P21-23. Animal were fed with cyclosporine water through the entire experiment. At postnatal day 90-95, visual function was tested by recording ERG, optokinetic response (OKR) and luminance thresholds from the superior colliculus. The second injection of hNPC was performed on the fellow eye after functional examination. Blood samples were collected at several time points after the second grafting. OKR and ERG were conducted weekly until the end of experiment.
Subretinal injection of hNPC significantly preserved visual function over untreated controls as measured by ERG, OKR and luminance threshold recordings. After the second injection of hNPC, visual function as tested by OKR was maintained the same as before the second injection (0.549 cycle/degree vs. 0.553 cycle/degree). Histological examine on retinal sections at early time point showed normal retinal lamination; there is no abnormal changes on cresyl violet stained sections.
This study showed redosing stem cells did not trigger acute rejection of the previous grafts. A long-term follow-up is needed to examine host immune response to the second grafts and the efficacy from the first graft on vision protection.
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