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Editors Selection IGR 16-4

Basic Research Animal Studies: Differentiation of iPS cells into RGC-like cells

Comment by Keith Martin on:

26985 Generation of retinal ganglion-like cells from reprogrammed mouse fibroblasts., Chen M; Chen Q; Sun X et al., Investigative Ophthalmology and Visual Science, 2010; 51: 5970-5978

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One of the key hopes for glaucoma therapy in the future is that lost retinal ganglion cells could be replaced. Stem cell treatments are a focus of great interest in this regard, but ethical issues with the use of embryonic stem cells persist. The discovery that mature adult cells can be reprogrammed to generate inducible pluripotent (iPS) cells with many of the characteristics of embryonic stem cells has been an exciting advance, but proof that iPS could form RGC has been limited.

In their intriguing recent paper, Chen et al. (1587) demonstrate that iPS cells can be differentiated to form cells with RGC-like features that express many of the markers of the mature RGC including Thy1.2, Brb3 and islet 1. It is interesting that the process required to generate RGC-like cells from iPS appears relatively straightforward: addition of a Wnt inhibitor (Dkk1), a BMP inhibitor (Noggin) and overexpression of the Math5

(a transcription factor important in RGC specification during retinal development). The authors have characterized the RGC-like cells carefully and the experimental work is nicely done. However, there are a number of issues that require further work. In particular, the proportion of cells that expressed Thy1.2, a key RGC marker, was very low. Better understanding of relevant transcriptional switches may improve yield in the future. In addition, several of the eyes transplanted with the iPS-derived cells developed teratomas, a common problem with current iPS techniques, though one that will hopefully become less of an issue as alternatives to viral induction of iPS continue to develop.

Finally, iPS-derived cells were able to survive but not to integrate when transplanted into the normal retina. Thus, a greater understanding of the barriers to cellular integration into the retina remains a key priority.

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