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Our
laboratory is interested in the molecular mechanisms underlying
retinal development, because we believe such knowledge bears
clinical implications as it might lead to genes capable of
inducing the genesis of retinal neurons for tissue or cell
replacement therapies. Our studies show that, in the chick
retina, a bHLH gene, neuroD, plays an instrumental
role in photoreceptor cell specification. When over-expressed
in the developing retina, neuroD promotes the overproduction
of photoreceptor cells. When ectopically expressed in cultured
chick RPE cells (non-neuronal cells), neuroD induces
de novo generation of cells that resemble photoreceptor cells
morphologically and molecularly. Recently, we observed that
different types of retinal neurons, including photoreceptor
cells and ganglion cells, can be generated de novo from cultured
RPE cells under the induction of another bHLH gene, neurogenin2.
These studies provide insight into the developmental pathways
leading to the differentiation of retinal neurons and may
also ultimately benefit the development of cell replacement
therapies.

Test-tube
retinal neurons. A: Clusters of
photoreceptor cells that were generated de novo from RPE cell
culture under the induction of a neurogenic gene. B:
Higher magnification of individual photoreceptor cells generated
as in A. Note that these cells have elaborate
cellular differentiation, including outer-segment like process
(arrowhead), axons (arrows), and axonal arboration (open arrowhead).
C: Cells that express two retinal ganglion
cell markers, one in red and the other in green.
Acknowledgements
Our studies are supported by NIH/NEI grant EY11640, EyeSight
Foundation of Alabama grant 01-7, and Research to Prevent
Blindness Dolly Green Scholar Award.
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