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Jian Ge, Ying Liu, Huiling Hu, Fei Deng; Retinal Neuron Derived from WERI-Rb1 Improve Visual Function of RD1 and DBA/2J Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2223. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Increasing evidence indicate that one of the pathway to isolate retinal progenitor cells(RPCs) from human retinalblastoma (hRb). This study was designed to determine if hRb (WERI-Rb1) can be directly induced into retinal photoreceptor cells and retinal ganglion cells(RGCs), and if the visual function mice might be improved in RD1 and DBA/2J by integrated transplantation of WERI-Rb1-derived cells and chondroitinase ABC.
Firstly the retinal progenitor cells-related characteristics of WERI-Rb1 were tested by gene and protein expression.Then WERI-Rb1 were induced to transdifferentiated into retinal photoreceptor cell-like cells by the addtion of DKK-1+Lefty-A, and into RGCs by add DKK-1+Noggin and overexpress of ATOH7. After digital gene expression tag profiling,immunofluorescence and western-blot analyses of WERI-Rb1-derived cells, each type of induced cells were injected into the subretinal space of RD1 mice or the vitreous space of DBA/2J mice combined with chondroitinase ABC. Immunohistochemistry was used to investigate the migration and integration of WERI-Rb1-derived cells, electroretinogram (ERG) was taken to evaluate visual functional improvement of the receptor mice.
WERI-Rb1 cells inherently express RPC-related genes such as Pax6,Otx2,Rax2 and Nestin. The addition of DL,DN and ATOH7 overexpression can transdifferentiate WERI-Rb1 cells into retinal photoreceptor cell-like cells and RGC-like cells, which not only display short axon-like process, but also express numrous genes and proteins related to retinal photoreceptor cells(Rcvrn,Rho,GFAP,PDC.etc.) and RGCs( Map-2,Isl-1,Brn-3b,Syp,SYT15,β- TUB.etc.). Moreover, WERI-Rb1-derived cells can survive and more cells migarated in retina when transplanted together with chondroitinase ABC into RD1 and DBA/2J mice. 4 weeks later, the mice visual fuction were improved somewhat.
Human Rb cells can be directly induced into retinal photoreceptor cells and RGCs.Visual function of receptor mice could be improved by combined transplant the cells with chondroitinase ABC. These preliminary results offer a new insight into the replacement therapy of inreversible retinal impairment by retinal neuron from human retinoblastoma.
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