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R.–T. Yan, W. Ma, W. Mao, L. Liang, S.–Z. Wang; Towards Producing Retinal Neurons from RPE: RPE Transdifferentiation is Not Biased Towards Photoreceptor Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2964.
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Our laboratory is interested in inducing de novo retinal neurogenesis in otherwise non–neural, cultured RPE cells. This study aims to determine whether cultured RPE cells are intrinsically biased towards photoreceptor cells or they can transdifferentiate towards other types of retinal neurons under appropriate guidance.
Several growth factors and >20 genes known to play instrumental roles in the development of the eye/retina/photoreceptors were assayed for their abilities to induce RPE transdifferentiation towards the various types of retinal neurons. E6 chick RPE was isolated, and its cells dissociated and cultured in the presence or absence of a growth factor or infected with a retrovirus expressing a particular gene. Later, cells in the culture were fixed and analyzed for neural properties at the molecular and morphological levels.
We found that cultured RPE cells could be guided to transdifferentiate towards different types of retinal neurons, including ganglion cells, amacrine cells, and photoreceptor cells. Among the genes/factors, three were found to initiate RPE transdifferentiation towards ganglion cells, two initiated RPE transdifferentiation towards non–photoreceptor neurons resembling amacrine cells, and neuroD and its three seemingly upstream genes induced RPE transdifferentiation towards photoreceptor cells. None of the five growth factors assayed induced a photoreceptor phenotype. We have also compared, and found no changes in, the outcomes of RPE transdifferentiation after grafting the cells into developing eyes.
These results indicate that with appropriate genes/factors RPE cells can be guided to transdifferentiate towards a discrete type of retinal neurons, including photoreceptor cells, but they are not intrinsically biased towards photoreceptors.
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