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Originally published In Press as doi:10.1167/iovs.09-3822 on July 23, 2009
 (Investigative Ophthalmology and Visual Science. 2010;51:516-525.)
© 2010 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.09-3822
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Using neurogenin to Reprogram Chick RPE to Produce Photoreceptor-like Neurons

Xiumei Li,1,2 Wenxin Ma,2 Yehong Zhuo,1 Run-Tao Yan,2 and Shu-Zhen Wang2

From the 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; and the 2Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama.

Corresponding author: Shu-Zhen Wang, Department of Ophthalmology, University of Alabama at Birmingham, 700 South 18th Street, Birmingham, AL 35294-0009; szwang{at}uab.edu.

Purpose. One potential therapy for vision loss from photoreceptor degeneration is cell replacement, but this approach presents a need for photoreceptor cells. This study explores whether the retinal pigment epithelium (RPE) could be a convenient source of developing photoreceptors.

Methods. The RPE of chick embryos was subjected to reprogramming by proneural genes neurogenin (ngn)1 and ngn3. The genes were introduced into the RPE through retrovirus RCAS-mediated transduction, with the virus microinjected into the eye or added to retinal pigment epithelial explant culture. The retinal pigment epithelia were then analyzed for photoreceptor traits.

Results. In chick embryos infected with retrovirus RCAS-expressing ngn3 (RCAS-ngn3), the photoreceptor gene visinin (the equivalent of mammalian recoverin) was expressed in cells of the retinal pigment epithelial layer. When isolated and cultured as explants, retinal pigment epithelial tissues from embryos infected with RCAS-ngn3 or RCAS-ngn1 gave rise to layers of visinin-positive cells. These reprogrammed cells expressed genes of phototransduction and synapses, such as red opsin, the {alpha}-subunit of cone transducin, SNAP-25, and PSD-95. Reprogramming occurred with retinal pigment epithelial explants derived from virally infected embryos and with retinal pigment epithelial explants derived from normal embryos, with the recombinant viruses added at the onset of the explant culture. In addition, reprogramming took place in retinal pigment epithelial explants from both young and old embryos, from embryonic day (E)6 to E18, when the visual system becomes functional in the chick.

Conclusions. The results support the prospect of exploring the RPE as a convenient source of developing photoreceptors for in situ cell replacement.






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