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T. Kiyama, S. W. Wang; Negative Feedback Restricts Neural Cell Production in the Retinal-Ciliary Margin of Adult Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2653.
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It is not clear whether a mammalian retina contains a proliferative region similar to the ciliary margin zone (CMZ) of an aquatic vertebrate. Our study showed that cells continue to proliferate at the retinal-ciliary margin in challenged mouse retinas indicating a potential that cell cycle can be reactivated in the region. Therefore, we hypothesize that the mammalian retinal-ciliary margin retains proliferative potency and proliferation can be triggered by retinal shortages. Based on the paradigm that a specific retinal cell type inhibits the formation of the same type, we followed the response of the retinal-ciliary margin of mouse retnas with different degrees of retinal ganglion cell (RGC) loss at different developmental and adult stages.
To test the hypothesis, we traced the response of retinal-ciliary margin in a series of retinas with a spectrum of RGC loss. Cell proliferation, marked by BrdU and phosphohistone-3, as well as the activity of math5, a gene essential for RGC production, were examined at given different points.
The math5 activity was prolonged to different degrees in the retinal-ciliary margin corresponding to the severity of RGC loss. Briefly, the less there are the RGCs, the longer the math5 is active in the retinal-ciliary margin. Also, we found that most cells in the ciliary margin are proliferative up to one month old, the latest time point we have examined.
Cells in the mouse retinal-ciliary margin retains the proliferative potential. Such a potential can be activated by lifting inhibition suggesting RGCs generate a negative feedback circuit for the production of new neurons.
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