Journal
JOURNAL OF COMPARATIVE NEUROLOGY
Volume 518, Issue 4, Pages 526-546Publisher
WILEY
DOI: 10.1002/cne.22236
Keywords
retina; reprogramming; Ca2+ imaging; light response
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Funding
- National Institutes of Health/National Eye Institute [EY11640]
- Eyesight Foundation [FY2008-09-134]
- China Scholarship Council
- Research to Prevent Blindness
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Photoreceptors are highly specialized sensory neurons in the retina, and their degeneration results in blindness. Replacement with developing photoreceptor cells promises to be an effective therapy, but it requires a supply of new photoreceptors, because the neural retina in human eyes lacks regeneration capability. We report efficient generation of differentiating, photoreceptor-like neurons from chick retinal pigment epithelial (RPE) cells propagated in culture through reprogramming with neurogenin1 (ngn1). In reprogrammed culture, a large number of the cells (85.0% +/- 5.9%) began to differentiate toward photoreceptors. Reprogrammed cells expressed transcription factors that set in motion photoreceptor differentiation, including Crx, Nr2E3, NeuroD, and RXR gamma, and phototransduction pathway components, including transducin, cGMP-gated channel, and red opsin of cone photoreceptors (equivalent to rhodopsin of rod photoreceptors). They developed inner segments rich in mitochondria. Furthermore, they responded to light by decreasing their cellular free calcium (Ca2+) levels and responded to 9-cis-retinal by increasing their Ca2+ levels after photobleaching, hallmarks of photoreceptor physiology. The high efficiency and the advanced photoreceptor differentiation indicate ngn1 as a gene of choice to reprogram RPE progeny cells to differentiate into photoreceptor neurons in future cell replacement studies. J. Comp. Neurol. 518:526-546, 2010. (C) 2009 Wiley-Liss, Inc
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